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Li R, Sun X, Yu Z, Zhu X, Zhao X, Li P, Liu N. Defining Optimal Lymph Node Yield in Gastrectomy: A Real-World Cohort Analysis. World J Surg Oncol 2025; 23:141. [PMID: 40217295 PMCID: PMC11992801 DOI: 10.1186/s12957-025-03787-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 03/29/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) has a high global mortality and incidence rate. Lymph node (LN) invasion is crucial in TNM staging, and an accurate LN staging system is vital for treatment decisions. However, the appropriate number of examined LNs remains uncertain. METHODS We retrospectively analyzed consecutive GC patients who underwent gastrectomy at the First Medical Center of the Chinese PLA General Hospital from January 2010 to December 2023. A new statistical model based on the β-binomial distribution and maximum likelihood method in R software was employed to calculate false-negative probabilities. RESULTS A total of 6463 GC patients were included. For cT1 patients, even with only five LNs excised, the likelihood of encountering occult positive LNs remained below 5%. For cT2 patients, 17 nodes were needed to rule out occult nodal disease with 90% confidence. While for cT3 and cT4 patients, even after the removal of 35 LNs, the likelihood of overlooking a positive node was still above 20%. Considering surgical extent, 25 nodes were required for patients who underwent proximal gastrectomy or distal gastrectomy to rule out occult nodal disease with 90% confidence, whereas those who received entire gastrectomy needed 59 nodes to achieve the same level of confidence. CONCLUSION Our study establishes a novel quantitative framework linking LN harvest thresholds to false-negative metastasis risk in GC, derived from real-world clinicopathological data.
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Affiliation(s)
- Rui Li
- School of Medicine, Nankai University, Tianjin, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, China
| | - Xu Sun
- School of Medicine, Nankai University, Tianjin, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, China
| | - Zhiyuan Yu
- School of Medicine, Nankai University, Tianjin, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, China
| | - Xiangchao Zhu
- Department of Gastrointestinal Surgery, Zibo Central Hospital, Zibo, China
| | - Xudong Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, China
| | - Peiyu Li
- School of Medicine, Nankai University, Tianjin, China.
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
- Medical School of Chinese PLA, Beijing, China.
| | - Na Liu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
- Medical School of Chinese PLA, Beijing, China.
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Ding L, Zhou M, Yin J, Zhang X, Ye Q, Qian N. Association of Antibiotic Used During Surgery With the Outcome in Stage I-III Gastric Cancer. Cancer Control 2025; 32:10732748251339261. [PMID: 40294379 PMCID: PMC12038211 DOI: 10.1177/10732748251339261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/02/2025] [Accepted: 04/16/2025] [Indexed: 04/30/2025] Open
Abstract
Introduction: The use of antibiotic (Abx) is common in gastric cancer (GC) patients undergoing radical resection; however, the prognostic value of the use of these agents in stage I-III patients remains largely unknown.Methods: Data concerning the use of Abx in GC patients during surgery including the cumulative defined daily dose (cDDD) and types of Abx, were collected retrospectively. Differences in clinical features between cDDD subgroups and type subgroups were compared. Overall survival (OS) differences were tested via the Kaplan-Meier method, and risk factors for survival were validated by a Cox proportional hazards model.Results: Of 162 patients enrolled, 81 were assigned to the low-cDDD and 81 to the high-cDDD group. Among them, 19 patients were assigned to ≤2 types and 143 to ≥3 types. The low- and high-cDDD subgroups of patients presented no significant difference in OS (log rank = 2.21, P = 0.137). Patients receiving ≥3 types presented significantly better OS (log rank = 4.58, P = 0.032) than those receiving ≤2 types. The low- and high-cDDD subgroups (log rank = 3.83, P = 0.050), but not the ≤2 and ≥3 type subgroups (log rank<0.01, P = 0.982), presented a significant difference in OS in patients undergoing total gastrectomy. These differences were maintained in patients without total gastrectomy (cDDD: log rank = 7.92, P = 0.005; types: log rank = 6.52, P = 0.011). The use of multiple Abx types was validated as an independent factor for OS (HR = 0.46, 95% CI: 0.24-0.90; P = 0.024).Conclusions: Abx use during surgery in patients with stage I-III GC may potentially correlate with the prognosis. Patients with ≥3 types of Abx were more likely to have good outcomes, particularly in those without total gastrectomy.
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Affiliation(s)
- Lijuan Ding
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, Sanya, P.R. China
- Chinese PLA Medical School, Beijing, P.R. China
| | - Mengyu Zhou
- Department of Emergency, Hainan Hospital of Chinese PLA General Hospital, Sanya, P.R. China
| | - Jiahui Yin
- Department of Urology, Hainan Hospital of Chinese PLA General Hospital, Sanya, P.R. China
| | | | - Qianwen Ye
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, Sanya, P.R. China
| | - Niansong Qian
- Senior Department of Thoracic Oncology, Respiratory and Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, P.R. China
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Yu Z, Liang C, Li R, Xu Q, Gao J, Li P, Zhou S, Zhao X, Xu M, Liang W. The impact of diabetes mellitus on short and long term outcomes in patients with gastric cancer following radical surgery: a retrospective cohort study with propensity score matching. BMC Cancer 2024; 24:1461. [PMID: 39604929 PMCID: PMC11603664 DOI: 10.1186/s12885-024-13232-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 11/22/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The objective of this study was to analyze the impact of diabetes mellitus (DM) on short and long term outcomes following radical gastrectomy using propensity score matching (PSM) method, as well as to further investigate the factors influencing patient survival post-radical gastrectomy. METHODS The patients who underwent radical gastrectomy for gastric cancer (GC) between January 2011 and December 2015 were selected as study population, and PSM procedure was conducted with a matching ratio of 1:3 between the DM and non-DM groups. The short-term recovery and long-term survival outcomes were compared between the DM and non-DM group. Subsequently, univariate and multivariate COX regression analyses were conducted to further explore the factors that influence survival outcomes. RESULTS Among the cohort of 2508 GC patients who underwent radical surgery prior to PSM, a total of 295 (11.8%) individuals were diagnosed with DM. After conducting 1:3 PSM, 293 DM patients and 821 control patients were enrolled. The results of comparative analysis revealed that the DM group exhibited a significantly higher rate of overall complications (P < 0.001), grade III-V complications (P = 0.010), and prolonged hospitalization (P = 0.001) compared to the control group. However, no statistical difference was observed in survival outcomes between the two groups. Besides, age > 65years (P < 0.001), BMI < 18.5 kg/m2 (P = 0.001), tumor size > 5 cm (P < 0.001), higher T (P = 0.012) and N tumor stage (P < 0.001), and the occurrence of severe complications (P = 0.007) were identified as independent risk factors for overall survival (OS). CONCLUSIONS The presence of combined DM in GC patients can heighten the susceptibility to postoperative complications and protract the duration of postoperative recovery, while exerting no significant impact on OS. This study also explored the predictors for OS, thereby providing valuable guidance for the perioperative management and postoperative monitoring.
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Affiliation(s)
- Zhiyuan Yu
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, China
| | - Chen Liang
- Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Rui Li
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, China
| | - Qixuan Xu
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Jingwang Gao
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Peiyu Li
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, China
| | - Sixin Zhou
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Xudong Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
| | - Manman Xu
- Fourth Department of Liver Disease, Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing You'an Hospital, Capital Medical University, No.8 Xitou Tiao Road Youwai Street, Beijing, 100069, China.
| | - Wenquan Liang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
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Li Q, Zhang C, Ren Y, Qiao L, Xu S, Li K, Liu Y. A novel platelets-related gene signature for predicting prognosis, immune features and drug sensitivity in gastric cancer. Front Immunol 2024; 15:1477427. [PMID: 39606245 PMCID: PMC11599260 DOI: 10.3389/fimmu.2024.1477427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 10/25/2024] [Indexed: 11/29/2024] Open
Abstract
Background Platelets can dynamically regulate tumor development and progression. Nevertheless, research on the predictive value and specific roles of platelets in gastric cancer (GC) is limited. This research aims to establish a predictive platelets-related gene signature in GC with prognostic and therapeutic implications. Methods We downloaded the transcriptome data and clinical materials of GC patients (n=378) from The Cancer Genome Atlas (TCGA) database. Prognostic platelets-related genes screened by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a risk model. Kaplan-Meier curves and receiver operating characteristic curves (ROCs) were performed in the TCGA cohort and three independent validation cohorts. A nomogram integrating the risk score and clinicopathological features was constructed. Functional enrichment and tumor microenvironment (TME) analyses were performed. Drug sensitivity prediction was conducted through The Cancer Therapeutics Response Portal (CTRP) database. Finally, the expression of ten signature genes was validated by quantitative real-time PCR (qRT-PCR). Results A ten-gene (SERPINE1, ANXA5, DGKQ, PTPN6, F5, DGKB, PCDH7, GNG11, APOA1, and TF) predictive risk model was finally constructed. Patients were categorized as high- or low-risk using median risk score as the threshold. The area under the ROC curve (AUC) values for the 1-, 2-, and 3-year overall survival (OS) in the training cohort were 0.670, 0.695, and 0.707, respectively. Survival analysis showed a better OS in low-risk patients in the training and validation cohorts. The AUCs of the nomogram for predicting 1-, 2-, and 3-year OS were 0.708, 0.763, and 0.742, respectively. TME analyses revealed a higher M2 macrophage infiltration and an immunosuppressive TME in the high-risk group. Furthermore, High-risk patients tended to be more sensitive to thalidomide, MK-0752, and BRD-K17060750. Conclusion The novel platelets-related genes signature we identified could be used for prognosis and treatment prediction in GC.
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Affiliation(s)
| | | | | | | | | | | | - Ying Liu
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
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Yu Z, Liu H, Li R, Hu L, Xiao C, Gao Y, Li P, Liang W, Zhou S, Zhao X. Clinicopathological Factors and Nomogram Construction for Lymph Node Metastasis in Locally Advanced Gastric Cancer. Cancer Manag Res 2024; 16:1475-1489. [PMID: 39439918 PMCID: PMC11495200 DOI: 10.2147/cmar.s487247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 10/15/2024] [Indexed: 10/25/2024] Open
Abstract
Background The research on lymph node metastasis (LNM) in locally advanced gastric cancer (LAGC) infiltrating the subserous tissue and serous membrane (T3-4a) is significantly inadequate. This study aims to explore the clinicopathological factors related to LNM in stages T3 and T4a LAGC, while also developing predictive nomograms. Methods After systematic searching and rigorous screening, 1995 T3 and 1244 T4a LAGC cases who underwent surgery without neoadjuvant or perioperative chemotherapy were selected. The risk factors associated with LNM were identified using both univariate and multivariate logistic regression analyses. Subsequently, the independent variables identified through the multivariate analyses were utilized to construct a nomogram. Results The incidence of LNM in T3 and T4a LAGC was 77.1% (1539/1995) and 83.8% (1043/1244), respectively. The following factors were found to be independently associated with LNM in T3 LAGC: preoperative serum albumin <41g/L (P=0.007), gastrointestinal obstruction (P<0.001), tumor location (P=0.040), tumor size >4cm (P=0.002), mixed (P=0.001) and undifferentiated histological types (P=0.002), presence of lymphovascular invasion (LVI) (P<0.001) and nerve invasion (P<0.001). Additionally, in T4a LAGC cases, serum albumin < 39g/L (P=0.004), tumor size >6cm (P=0.020), mixed (P<0.001) and undifferentiated histological types (P<0.001), presence of gastrointestinal hemorrhage (P=0.016), neuroendocrine differentiation (P=0.024), and LVI (P<0.001) independently influenced the occurrence of LNM. Conclusion This study identified the risk factors associated with LNM in T3-4a LAGC cases and constructed nomograms, thereby providing valuable guidance for formulating and implementing a multidisciplinary perioperative treatment program.
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Affiliation(s)
- Zhiyuan Yu
- Medical School of Chinese PLA, Beijing, People’s Republic of China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
- School of Medicine, Nankai University, Tianjin, People’s Republic of China
| | - Haopeng Liu
- Department of Hepatobiliary Surgery, Zhangqiu District People’s Hospital, Jinan, Shandong Province, People’s Republic of China
| | - Rui Li
- Medical School of Chinese PLA, Beijing, People’s Republic of China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
- School of Medicine, Nankai University, Tianjin, People’s Republic of China
| | - Liai Hu
- School of Medicine, Nankai University, Tianjin, People’s Republic of China
| | - Chun Xiao
- Department of General Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China
| | - Yunhe Gao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Peiyu Li
- Medical School of Chinese PLA, Beijing, People’s Republic of China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
- School of Medicine, Nankai University, Tianjin, People’s Republic of China
| | - Wenquan Liang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Sixin Zhou
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Xudong Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Yu Z, Liang C, Xu Q, Li R, Gao J, Gao Y, Liang W, Li P, Zhao X, Zhou S. Analysis of postoperative complications and long term survival following radical gastrectomy for patients with gastric cancer. Sci Rep 2024; 14:23869. [PMID: 39396097 PMCID: PMC11470947 DOI: 10.1038/s41598-024-74758-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/30/2024] [Indexed: 10/14/2024] Open
Abstract
This study aimed to analyze the complications and long-term survival outcomes in patients who underwent radical gastrectomy for gastric cancer, as well as to identify the risk factors associated with postoperative complications. After conducting a comprehensive search within the medical records system, a total of 2508 patients who underwent radical gastrectomy and met the inclusion criteria were enrolled. Of the 2508 patients, 301 were diagnosed with postoperative complications. The pathological data, postoperative recovery, and survival outcome were compared between complication and control group. Subsequently, univariate and multivariate logistic regression analyses were conducted to identified the risk factors. According to the Clavien-Dindo grading criteria for postoperative complications, the proportions of grade I, II, III, IV, and V complications following radical gastrectomy were observed to be 28.2%, 42.9%, 19.6%, 8.0%, and 1.3%, respectively. The presence of postoperative complications significantly prolonged the duration of gastrointestinal decompression (P < 0.001), catheter retention (P < 0.001), fasting (P < 0.001), and hospitalization (P < 0.001). Additionally, it had a detrimental impact on survival outcomes. Age > 65years [odds ratio (OR) = 1.378, P = 0.020], presence of diabetes (OR = 2.042, P < 0.001), operative duration > 215 min (OR = 1.450, P = 0.006), intraoperative blood loss > 275 ml (OR = 1.474, P = 0.004), and Roux-en-Y anastomosis for both whole stomach (OR = 1.567, P = 0.021) and distal gastric cancer (OR = 2.083, P = 0.003) were identified as independent risk factors for postoperative complications. This study analyzed the complications and survival outcomes following radical gastrectomy, and investigated the predictors for postoperative complications, thereby providing valuable guidance on the prevention and management of surgical complications in gastric cancer.
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Affiliation(s)
- Zhiyuan Yu
- School of Medicine, Nankai University, Tianjin, China
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Chen Liang
- Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Qixuan Xu
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Rui Li
- School of Medicine, Nankai University, Tianjin, China
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Jingwang Gao
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Yunhe Gao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Wenquan Liang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
| | - Peiyu Li
- School of Medicine, Nankai University, Tianjin, China.
- Medical School of Chinese PLA, Beijing, China.
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
| | - Xudong Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
| | - Sixin Zhou
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
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Yu Z, Liang C, Gao J, He P, Xu Q, Gao Y, Li P, Zhou S, Zhao X. Clinicopathologic factors correlated with lymph node metastasis in gastric cancer: a retrospective cohort study involving 5606 patients. J Gastrointest Surg 2024; 28:1242-1249. [PMID: 38744374 DOI: 10.1016/j.gassur.2024.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 05/07/2024] [Accepted: 05/10/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment programs. METHODS A total of 5606 patients with gastric cancer with comprehensive clinicopathologic data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be used for further analysis. Subsequently, univariate and multivariate logistic regression analyses were performed to identify the risk factors. RESULTS The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6%, respectively. Female (odds ratio [OR], 1.559; P = .032), lower tumor location (OR, 1.773; P = .023), tumor size of >2 cm (OR, 2.007; P < .001), mixed (OR, 2.371; P = .001) and undifferentiated histologic types (OR, 2.952; P < .001), T1b stage (OR, 2.041; P < .001), presence of ulceration (OR, 1.758; P = .027), and lymphovascular invasion (OR, 5.722; P < .001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in patients with EGC. CONCLUSION This study identified the clinicopathologic factors associated with LNM in patients with EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing patients with EGC.
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Affiliation(s)
- Zhiyuan Yu
- School of Medicine, Nankai University, Tianjin, China; Medical School of Chinese People's Liberation Army, Beijing, China; Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chen Liang
- First Department of Liver Disease/Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Jingwang Gao
- Medical School of Chinese People's Liberation Army, Beijing, China; Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Ping He
- School of Medicine, Nankai University, Tianjin, China; Medical School of Chinese People's Liberation Army, Beijing, China
| | - Qixuan Xu
- Medical School of Chinese People's Liberation Army, Beijing, China; Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yunhe Gao
- Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Peiyu Li
- School of Medicine, Nankai University, Tianjin, China; Medical School of Chinese People's Liberation Army, Beijing, China; Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Sixin Zhou
- Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xudong Zhao
- Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
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Islam W, Abdoli N, Alam TE, Jones M, Mutembei BM, Yan F, Tang Q. A Neoteric Feature Extraction Technique to Predict the Survival of Gastric Cancer Patients. Diagnostics (Basel) 2024; 14:954. [PMID: 38732368 PMCID: PMC11083029 DOI: 10.3390/diagnostics14090954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/26/2024] [Accepted: 04/28/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND At the time of cancer diagnosis, it is crucial to accurately classify malignant gastric tumors and the possibility that patients will survive. OBJECTIVE This study aims to investigate the feasibility of identifying and applying a new feature extraction technique to predict the survival of gastric cancer patients. METHODS A retrospective dataset including the computed tomography (CT) images of 135 patients was assembled. Among them, 68 patients survived longer than three years. Several sets of radiomics features were extracted and were incorporated into a machine learning model, and their classification performance was characterized. To improve the classification performance, we further extracted another 27 texture and roughness parameters with 2484 superficial and spatial features to propose a new feature pool. This new feature set was added into the machine learning model and its performance was analyzed. To determine the best model for our experiment, Random Forest (RF) classifier, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Naïve Bayes (NB) (four of the most popular machine learning models) were utilized. The models were trained and tested using the five-fold cross-validation method. RESULTS Using the area under ROC curve (AUC) as an evaluation index, the model that was generated using the new feature pool yields AUC = 0.98 ± 0.01, which was significantly higher than the models created using the traditional radiomics feature set (p < 0.04). RF classifier performed better than the other machine learning models. CONCLUSIONS This study demonstrated that although radiomics features produced good classification performance, creating new feature sets significantly improved the model performance.
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Affiliation(s)
- Warid Islam
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (W.I.); (N.A.)
| | - Neman Abdoli
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA; (W.I.); (N.A.)
| | - Tasfiq E. Alam
- School of Industrial and Systems Engineering, University of Oklahoma, Norman, OK 73019, USA;
| | - Meredith Jones
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (M.J.); (B.M.M.); (F.Y.)
| | - Bornface M. Mutembei
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (M.J.); (B.M.M.); (F.Y.)
| | - Feng Yan
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (M.J.); (B.M.M.); (F.Y.)
| | - Qinggong Tang
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (M.J.); (B.M.M.); (F.Y.)
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Jiang KL, Wang XX, Liu XJ, Guo LK, Chen YQ, Jia QL, Yang KM, Ling JH. Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis. World J Gastrointest Oncol 2024; 16:1626-1646. [PMID: 38660634 PMCID: PMC11037053 DOI: 10.4251/wjgo.v16.i4.1626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 01/18/2024] [Accepted: 02/29/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.
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Affiliation(s)
- Kai-Lin Jiang
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
| | - Xiang-Xiang Wang
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
| | - Xue-Jiao Liu
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
| | - Li-Kun Guo
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
| | - Yong-Qi Chen
- Department of Pathology, Shuguang Hospital, Shanghai 200021, China
| | - Qing-Ling Jia
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
| | - Ke-Ming Yang
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
| | - Jiang-Hong Ling
- Department of Gastroenterology, Shuguang Hospital, Shanghai 200021, China
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10
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Gao X, Li G, Deng J, Zhao L, Han W, Zhang N, Gao Y, Lu L, Wang S, Yu J, Yan J, Zhang G, Peng R, Zhang R, Fu Y, He F, Hu J, Wang W, Fan P, Si C, Gao P, Liang H, Chen H, Ji G, Shang L, Zhao Q, Zhang Z, Yang S, Wang Z, Xi H, Chen Y, Wu K, Nie Y. Association of survival with adjuvant chemotherapy in patients with stage IB gastric cancer: a multicentre, observational, cohort study. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2024; 45:101031. [PMID: 38361774 PMCID: PMC10867760 DOI: 10.1016/j.lanwpc.2024.101031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 12/25/2023] [Accepted: 01/25/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. METHODS We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. FINDINGS Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. INTERPRETATION In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. FUNDING National Natural Science Foundation of China; the National Key R&D Program of China.
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Affiliation(s)
- Xianchun Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
- Department of Health Statistics, School of Preventive Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Gang Li
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing 210009, China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Cancer for Cancer, West Huanhu Road, Tianjin 300060, China
| | - Lulu Zhao
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China
| | - Weili Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Nannan Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Yunhe Gao
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing, Beijing 100853, China
| | - Linbin Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Shibo Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Jun Yu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Junya Yan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Gan Zhang
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing, Beijing 100853, China
| | - Rui Peng
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing 210009, China
| | - Rupeng Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Cancer for Cancer, West Huanhu Road, Tianjin 300060, China
| | - Yu Fu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Shenyang, 110001, China
| | - Fang He
- Department of Gastroenterology, General Hospital of Ningxia Medical University, 804 Shengli, Yinchuan 750004, China
| | - Junguo Hu
- Gansu Wuwei Cancer Hospital, 16 Xuanwu, Wuwei 733000, China
| | - Wanqing Wang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China
| | - Ping Fan
- Gansu Wuwei Cancer Hospital, 16 Xuanwu, Wuwei 733000, China
| | - Cen Si
- Department of Gastroenterology, General Hospital of Ningxia Medical University, 804 Shengli, Yinchuan 750004, China
| | - Peng Gao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Shenyang, 110001, China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Cancer for Cancer, West Huanhu Road, Tianjin 300060, China
| | - Huanqiu Chen
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing 210009, China
| | - Gang Ji
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Lei Shang
- Department of Health Statistics, School of Preventive Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Qingchuan Zhao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Zhiyi Zhang
- Gansu Wuwei Cancer Hospital, 16 Xuanwu, Wuwei 733000, China
| | - Shaoqi Yang
- Department of Gastroenterology, General Hospital of Ningxia Medical University, 804 Shengli, Yinchuan 750004, China
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Shenyang, 110001, China
| | - Hongqing Xi
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing, Beijing 100853, China
| | - Yingtai Chen
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China
| | - Kaichun Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China
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11
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Liu T, Feng Y, Yang S, Ge Y, Zhang T, Li J, Li C, Ruan Y, Luo B, Liang G. Depicting the Profile of METTL3-Mediated lncRNA m6A Modification Variants and Identified SNHG7 as a Prognostic Indicator of MNNG-Induced Gastric Cancer. TOXICS 2023; 11:944. [PMID: 37999596 PMCID: PMC10674297 DOI: 10.3390/toxics11110944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/14/2023] [Accepted: 11/15/2023] [Indexed: 11/25/2023]
Abstract
As a representative example of an environmental chemical carcinogen, MNNG exposure is closely associated with the onset of gastric cancer (GC) where N6-methyladenosine (m6A) RNA methylation tends to be the critical epigenetic event. However, the effect of m6A modification on long non-coding RNAs (lncRNAs) in MNNG-induced GC onset is still unclear. To address the above issue, based on the Methylated RNA immunoprecipitation sequencing (MeRIP-seq) data of MNNG-induced malignant cells (MCs) and GC cells, we comprehensively analyzed the MNNG exposure-associated vital lncRNAs. MeRIP-seq analysis identified 1432 lncRNA transcripts in the MC cell, and 3520 lncRNA transcripts were found to be m6A modified in the GC cell, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that MNNG exposure could spark cellular localization change, which might be the critical cellular note variation for malignant transformation. We demonstrated that METTL3 is responsible for N6 methylation of lncRNAs and identified SNHG7 as a downstream target of METTL3. More importantly, we observed that SNHG7 was progressively up-regulated during gastric carcinogenesis by MNNG exposure. Finally, we investigated SNHG7 expression in different stages of GC malignancies and found that elevated SNHG7 expression correlated with advanced clinical features and poor prognosis in GC. In conclusion, our study found for the first time that METTL3 regulates the m6A methylation level of lncRNA SNHG7 and its expression in MNNG exposure-induced GC, suggesting that SNHG7 as a predictive biomarker or therapeutic target for GC.
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Affiliation(s)
- Tong Liu
- Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou 730000, China; (T.L.); (C.L.); (Y.R.); (B.L.)
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
| | - Yanlu Feng
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
| | - Sheng Yang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
| | - Yiling Ge
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
| | - Tianyi Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
| | - Jie Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
| | - Chengyun Li
- Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou 730000, China; (T.L.); (C.L.); (Y.R.); (B.L.)
| | - Ye Ruan
- Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou 730000, China; (T.L.); (C.L.); (Y.R.); (B.L.)
| | - Bin Luo
- Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou 730000, China; (T.L.); (C.L.); (Y.R.); (B.L.)
| | - Geyu Liang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; (Y.F.); (S.Y.); (Y.G.); (T.Z.); (J.L.)
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12
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Li Y, Li S, Liu L, Zhang LY, Wu D, Xie TY, Wang XX. Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer. World J Gastrointest Oncol 2023; 15:1605-1615. [PMID: 37746641 PMCID: PMC10514718 DOI: 10.4251/wjgo.v15.i9.1605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/15/2023] [Accepted: 08/02/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND The current prognostic significance of perigastric tumor deposits (TDs) in gastric cancer (GC) remains unclear. AIM To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC. METHODS This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1, 2012 to December 31, 2017 at the Chinese PLA General Hospital. According to the presence of perigastric TDs or not, the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching. The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling. The Kaplan-Meier method was used to plot survival curves. Multivariate Cox regression modeling and the log-rank test were used to analyze the data. RESULTS Perigastric TDs were found to be positive in 339 (5.09%) of the 6672 patients with GC, among whom 237 were men (69.91%) and 102 were women (30.09%) (2.32:1). The median age was 59 years (range, 27 to 78 years). Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients (P < 0.05). The 1-, 3-, and 5-year overall survival rates of GC patients with TDs were 68.3%, 19.6%, and 11.2%, respectively, and these were significantly poorer than those without TDs of the same stages. There was significant variation in survival according to TD locations among the GC patients (P < 0.05). A new TNM staging framework for GC was formulated according to TD location. When TDs appear in the gastric body, the original stages T1, T2, and T3 are classified as T4a with the new framework, and the original stages T4a and T4b both are classified as T4b. When TDs appear in the lesser curvature, the previous stages N0, N1, N2, and N3 now both are classified as N3. When TDs appear in the greater curvature or the distant tissue, the patient should be categorized as having M1. With the new GC staging scheme including TDs, the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs. CONCLUSION TDs are a poor prognostic factor for patients with primary GC. The location of TDs is associated with the prognosis of patients with primary GC. Accordingly, we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.
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Affiliation(s)
- Yang Li
- Medical School of Chinese People's Liberation Army, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Shuo Li
- Medical School of Chinese People's Liberation Army, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Lu Liu
- Medical School of Chinese People's Liberation Army, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Li-Yu Zhang
- Medical School of Chinese People's Liberation Army, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Di Wu
- Medical School of Chinese People's Liberation Army, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Tian-Yu Xie
- Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Xin-Xin Wang
- Department of General Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China
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13
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Li Y, Shen L, Tao K, Xu G, Ji K. Key Roles of p53 Signaling Pathway-Related Factors GADD45B and SERPINE1 in the Occurrence and Development of Gastric Cancer. Mediators Inflamm 2023; 2023:6368893. [PMID: 37662480 PMCID: PMC10471451 DOI: 10.1155/2023/6368893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 05/16/2023] [Accepted: 07/24/2023] [Indexed: 09/05/2023] Open
Abstract
p53 can function as an independent and unfavorable prognosis biomarker in cancer patients. We tried to identify the key factors of the p53 signaling pathway involved in gastric cancer (GC) occurrence and development based on the genotype-tissue expression (GTEx) and the Cancer Genome Atlas (TCGA) screening. We downloaded gene expression data and clinical data of GC included in the GTEx and TCGA databases, followed by differential analysis. Then, the key factors in the p53 signaling pathway were identified, followed by an analysis of the correlation between key factors and the prognosis of GC patients. Human GC cell lines were selected for in vitro cell experiments to verify the effects of key prognostic factors on the proliferation, migration, invasion, and apoptosis of GC cells. We found 4,944 significantly differentially expressed genes (DEGs), of which 2,465 were upregulated and 2,479 downregulated in GC. Then, 27 DEGs were found to be involved in the p53 signaling pathway. GADD45B and SERPINE1 genes were prognostic high-risk genes. The regression coefficients of GADD45B and SERPINE1 were positive. GADD45B was poorly expressed, while SERPINE1 was highly expressed in GC tissues, highlighting their prognostic role in GC. The in vitro cell experiments confirmed that overexpression of GADD45B or silencing of SERPINE1 could inhibit the proliferation, migration, and invasion and augment the apoptosis of GC cells. Collectively, the p53 signaling pathway-related factors GADD45B and SERPINE1 may be key genes that participate in the development of GC.
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Affiliation(s)
- Yaoqing Li
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Liyijing Shen
- Department of Radiology, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Kelong Tao
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Guangen Xu
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Kewei Ji
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
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14
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Li X, Lin YL, Shao JK, Wu XJ, Li X, Yao H, Shi FL, Li LS, Zhang WG, Chang ZY, Chai NL, Wang YL, Linghu EQ. Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer. World J Gastroenterol 2023; 29:3482-3496. [PMID: 37389236 PMCID: PMC10303519 DOI: 10.3748/wjg.v29.i22.3482] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 05/04/2023] [Accepted: 05/11/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. AIM To identify a novel biomarker for early detection of GC. METHODS Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. RESULTS There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). CONCLUSION Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.
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Affiliation(s)
- Xiao Li
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Yan-Li Lin
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Jia-Kang Shao
- Medical School of Chinese PLA, Beijing 100853, China
| | - Xiao-Jie Wu
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Xiang Li
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - He Yao
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Fa-Liang Shi
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Long-Song Li
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | - Wen-Gang Zhang
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | | | - Ning-Li Chai
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - You-Liang Wang
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - En-Qiang Linghu
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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Wu J, Wang H, Yin X, Wang X, Wang Y, Lu Z, Zhang J, Zhang Y, Xue Y. Efficacy of Lymph Node Location-Number Hybrid Staging System on the Prognosis of Gastric Cancer Patients. Cancers (Basel) 2023; 15:cancers15092659. [PMID: 37174124 PMCID: PMC10177424 DOI: 10.3390/cancers15092659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/18/2023] [Accepted: 05/04/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Lymph node metastasis location and number significantly affects the prognosis of patients with gastric cancer (GC). This study was designed to examine a new lymph node hybrid staging (hN) system to increase the predictive ability for patients with GC. METHODS This study analyzed the gastrointestinal treatment of GC at the Harbin Medical University Cancer Hospital from January 2011 to December 2016, and selected 2598 patients from 2011 to 2015 as the training cohort (hN) and 756 patients from 2016 as the validation cohort (2016-hN). The study utilized the receiver operating characteristic curve (ROC), c-index, and decision curve analysis (DCA) to compare the prognostic performance of the hN with the 8th edition of AJCC pathological lymph node (pN) staging for GC patients. RESULTS The ROC verification of the training cohort and validation cohort based on each hN staging and pN staging showed that for each N staging, the hN staging had a training cohort with an AUC of 0.752 (0.733, 0.772) and a validation cohort with an AUC of 0.812 (0.780, 0.845). In the pN staging, the training cohort had an AUC of 0.728 (0.708, 0.749), and the validation cohort had an AUC of 0.784 (0.754, 0.824). c-Index and DCA also showed that hN staging had a higher prognostic ability than pN staging, which was confirmed in the training cohort and the verification cohort, respectively. CONCLUSION Lymph node location-number hybrid staging can significantly improve the prognosis of patients with GC.
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Affiliation(s)
- Junpeng Wu
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Hao Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Xin Yin
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Xibo Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Yufei Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Zhanfei Lu
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Jiaqi Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Yao Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
| | - Yingwei Xue
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
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Mao LT, Chen WC, Lu JY, Zhang HL, Ye YS, Zhang Y, Liu B, Deng WW, Liu X. Quantitative parameters in novel spectral computed tomography: Assessment of Ki-67 expression in patients with gastric adenocarcinoma. World J Gastroenterol 2023; 29:1458-1469. [DOI: 10.3748/wjg.v29.i10.1458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/10/2023] Open
Abstract
BACKGROUND The level of Ki-67 expression has served as a prognostic factor in gastric cancer. The quantitative parameters based on the novel dual-layer spectral detector computed tomography (DLSDCT) in discriminating the Ki-67 expression status are unclear.
AIM To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma (GC).
METHODS Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma. Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt (kev), the slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (nIC), effective atomic number (Zeff) and normalized Zeff (nZeff) in the arterial phase (AP) and venous phase (VP) were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma. Spearman’s correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups.
RESULTS Thirty-seven and 71 patients were classified as having low and high Ki-67 expression, respectively. CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, and Zeff-related parameters were significantly higher, but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status, and other analyzed parameters showed no statistical difference between the two groups. Spearman’s correlation analysis showed that CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, Zeff, and nZeff exhibited a negative correlation with Ki-67 status, whereas IC and nIC had positive correlation with Ki-67 status. The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status [area under the curve (AUC) = 0.967; sensitivity 95.77%; specificity 91.89%)]. Nevertheless, the differentiating capabilities of single-variable model were moderate (AUC value 0.630 - 0.835). In addition, the nZeffVP and nICVP (AUC 0.835 and 0.805) showed better performance than CT40 kev-VP, CT70 kev-VP and CT100 kev-VP (AUC 0.630, 0.631 and 0.662) in discriminating the Ki-67 status.
CONCLUSION Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma. Zeff and IC may be useful parameters for evaluating the Ki-67 expression.
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Affiliation(s)
- Li-Ting Mao
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Wei-Cui Chen
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Jian-Ye Lu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Han-Liang Zhang
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Yong-Song Ye
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Yu Zhang
- Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Bo Liu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Wei-Wei Deng
- Department of Scientific Research, Clinical & Technical Support, Philips Healthcare China, Shanghai 200040, China
| | - Xian Liu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
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Mao LT, Chen WC, Lu JY, Zhang HL, Ye YS, Zhang Y, Liu B, Deng WW, Liu X. Quantitative parameters in novel spectral computed tomography: Assessment of Ki-67 expression in patients with gastric adenocarcinoma. World J Gastroenterol 2023; 29:1602-1613. [PMID: 36970586 PMCID: PMC10037253 DOI: 10.3748/wjg.v29.i10.1602] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 12/23/2022] [Accepted: 01/16/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND The level of Ki-67 expression has served as a prognostic factor in gastric cancer. The quantitative parameters based on the novel dual-layer spectral detector computed tomography (DLSDCT) in discriminating the Ki-67 expression status are unclear.
AIM To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma (GC).
METHODS Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma. Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt (kev), the slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (nIC), effective atomic number (Zeff) and normalized Zeff (nZeff) in the arterial phase (AP) and venous phase (VP) were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma. Spearman’s correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups.
RESULTS Thirty-seven and 71 patients were classified as having low and high Ki-67 expression, respectively. CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, and Zeff-related parameters were significantly higher, but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status, and other analyzed parameters showed no statistical difference between the two groups. Spearman’s correlation analysis showed that CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, Zeff, and nZeff exhibited a negative correlation with Ki-67 status, whereas IC and nIC had positive correlation with Ki-67 status. The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status [area under the curve (AUC) = 0.967; sensitivity 95.77%; specificity 91.89%)]. Nevertheless, the differentiating capabilities of single-variable model were moderate (AUC value 0.630 - 0.835). In addition, the nZeffVP and nICVP (AUC 0.835 and 0.805) showed better performance than CT40 kev-VP, CT70 kev-VP and CT100 kev-VP (AUC 0.630, 0.631 and 0.662) in discriminating the Ki-67 status.
CONCLUSION Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma. Zeff and IC may be useful parameters for evaluating the Ki-67 expression.
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Affiliation(s)
- Li-Ting Mao
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Wei-Cui Chen
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Jian-Ye Lu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Han-Liang Zhang
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Yong-Song Ye
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Yu Zhang
- Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Bo Liu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
| | - Wei-Wei Deng
- Department of Scientific Research, Clinical & Technical Support, Philips Healthcare China, Shanghai 200040, China
| | - Xian Liu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
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Zhao YX, Ma LB, Yang Z, Wang F, Wang HY, Dang JY. Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin. World J Gastrointest Oncol 2023; 15:286-302. [PMID: 36908323 PMCID: PMC9994047 DOI: 10.4251/wjgo.v15.i2.286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/23/2022] [Accepted: 01/05/2023] [Indexed: 02/14/2023] Open
Abstract
BACKGROUND Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a newly discovered oncogene. It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer (GC) cells. CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies. The underlying mechanism, however, is unknown. Further, the primary treatment regimen for GC is oxaliplatin-based chemotherapy. Nonetheless, it often fails due to chemoresistance of GC cells to oxaliplatin.
AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.
METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues. CIP2A expression in GC cell lines was reduced using small interfering RNA. After confirming the silencing efficiency, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment. Further, the key genes and protein changes were verified using real-time quantitative reverse transcription PCR and Western blotting, respectively, before and after intervention. For bioinformatics analysis, we used the R software and Bioconductor project. For statistical analysis, we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0 (IBM, Armonk, United States).
RESULTS A high level of CIP2A expression was associated with tumor size, T stage, lymph node metastasis, Tumor Node Metastasis stage, and a poor prognosis. Further, CIP2A expression was higher in GC cells than in normal human gastric epithelial cells. Using small interfering RNA against CIP2A, we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin. Moreover, CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells. Hence, high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin. In human GC cells, CIP2A regulated protein kinase B phosphorylation, and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin. Therefore, the protein kinase B signaling pathway was correlated with CIP2A-enhanced chemoresistance of human GC cells to oxaliplatin.
CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.
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Affiliation(s)
- Yong-Xun Zhao
- The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Li-Bin Ma
- The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Ze Yang
- The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Fang Wang
- Department of Pathology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui-Ying Wang
- The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jia-Yao Dang
- The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
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Sierzega M, Bobrzynski L, Kolodziejczyk P, Wallner G, Kulig J, Szczepanik A, Sierzega M, Bobrzynski L, Kolodziejczyk P, Wallner G, Kulig J, Szczepanik A, Dadan J, Drews M, Fraczek M, Jeziorski A, Krawczyk M, Starzynska T, Richter P. Nomogram-Based Prognostic Evaluation of Gastric Cancer Patients with Low Counts of Examined Lymph Nodes Outperforms the Predictive Ability of the 7 th and 8 th Editions of the American Joint Committee on Cancer Staging System. J Gastrointest Surg 2023; 27:7-16. [PMID: 36138310 DOI: 10.1007/s11605-022-05334-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 04/09/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.
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Affiliation(s)
- Marek Sierzega
- First Department of Surgery, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688, Krakow, Poland.
| | - Lukasz Bobrzynski
- First Department of Surgery, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688, Krakow, Poland
| | - Piotr Kolodziejczyk
- First Department of Surgery, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688, Krakow, Poland
| | - Grzegorz Wallner
- Second Department of General, Gastrointestinal and Oncological Surgery of the Alimentary Tract, Medical University of Lublin, Lublin, Poland
| | - Jan Kulig
- First Department of Surgery, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688, Krakow, Poland
| | - Antoni Szczepanik
- First Department of Surgery, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688, Krakow, Poland
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Hao D, Li Q, Feng QX, Qi L, Liu XS, Arefan D, Zhang YD, Wu S. SurvivalCNN: A deep learning-based method for gastric cancer survival prediction using radiological imaging data and clinicopathological variables. Artif Intell Med 2022; 134:102424. [PMID: 36462894 DOI: 10.1016/j.artmed.2022.102424] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/15/2022] [Accepted: 10/07/2022] [Indexed: 12/13/2022]
Abstract
Radiological images have shown promising effects in patient prognostication. Deep learning provides a powerful approach for in-depth analysis of imaging data and integration of multi-modal data for modeling. In this work, we propose SurvivalCNN, a deep learning structure for cancer patient survival prediction using CT imaging data and non-imaging clinical data. In SurvivalCNN, a supervised convolutional neural network is designed to extract volumetric image features, and radiomics features are also integrated to provide potentially different imaging information. Within SurvivalCNN, a novel multi-thread multi-layer perceptron module, namely, SurvivalMLP, is proposed to perform survival prediction from censored survival data. We evaluate the proposed SurvivalCNN framework on a large clinical dataset of 1061 gastric cancer patients for both overall survival (OS) and progression-free survival (PFS) prediction. We compare SurvivalCNN to three different modeling methods and examine the effects of various sets of data/features when used individually or in combination. With five-fold cross validation, our experimental results show that SurvivalCNN achieves averaged concordance index 0.849 and 0.783 for predicting OS and PFS, respectively, outperforming the compared state-of-the-art methods and the clinical model. After future validation, the proposed SurvivalCNN model may serve as a clinical tool to improve gastric cancer patient survival estimation and prognosis analysis.
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Affiliation(s)
- Degan Hao
- Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Qiong Li
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Qiu-Xia Feng
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Liang Qi
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Xi-Sheng Liu
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Dooman Arefan
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Yu-Dong Zhang
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China.
| | - Shandong Wu
- Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15260, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15260, USA; Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
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Wang H, Yin X, Lou SH, Fang TY, Han BL, Gao JL, Wang YF, Zhang DX, Wang XB, Lu ZF, Wu JP, Zhang JQ, Wang YM, Zhang Y, Xue YW. Metastatic lymph nodes and prognosis assessed by the number of retrieved lymph nodes in gastric cancer. World J Gastrointest Surg 2022; 14:1230-1249. [PMID: 36504519 PMCID: PMC9727575 DOI: 10.4240/wjgs.v14.i11.1230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/17/2022] [Accepted: 10/20/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study.
AIM To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis.
METHODS This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes.
RESULTS A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (P = 0.044, P = 0.037, P = 0.003, P < 0.001).
CONCLUSION A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.
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Affiliation(s)
- Hao Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Xin Yin
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Sheng-Han Lou
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Tian-Yi Fang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Bang-Ling Han
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Jia-Liang Gao
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Yu-Fei Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Dao-Xu Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Xi-Bo Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Zhan-Fei Lu
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Jun-Peng Wu
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Jia-Qi Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Yi-Min Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Yao Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Ying-Wei Xue
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
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Chen Y, Chen Y, Wen L, Tou L, Wang H, Teng L. PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study. Front Surg 2022; 9:986696. [PMID: 36439539 PMCID: PMC9684711 DOI: 10.3389/fsurg.2022.986696] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/24/2022] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. METHODS Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. RESULTS Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. CONCLUSIONS Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.
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Affiliation(s)
- Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Liping Wen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Laizhen Tou
- Department of Gastrointestinal Surgery, Lishui Hospital, College of Medicine, Zhejiang University, Lishui, China
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Bai C, Chen DG. NRCAM acts as a prognostic biomarker and promotes the tumor progression in gastric cancer via EMT pathway. Tissue Cell 2022; 77:101859. [DOI: 10.1016/j.tice.2022.101859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/09/2022] [Accepted: 06/20/2022] [Indexed: 02/07/2023]
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Li T, Chen Y, Li Y, Chen G, Zhao Y, Su G. Antifibrotic effect of AD-1 on lipopolysaccharide-mediated fibroblast injury in L929 cells and bleomycin-induced pulmonary fibrosis in mice. Food Funct 2022; 13:7650-7665. [PMID: 35735105 DOI: 10.1039/d1fo04212b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
20(R)-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH3-PPD, AD-1) is a dammarane ginsenoside that is isolated from Panax notoginseng. The present study aimed to explore its anti-pulmonary fibrosis (PF) effect in vitro and in vivo. L929 cells were treated with 10 μg mL-1 lipopolysaccharide (LPS) to establish a PF model in vitro and mice were administered with 3.5 mg kg-1 bleomycin (BLM) by endotracheal intubation to establish a PF model in vivo for investigating the anti-PF effect and its potential mechanism. The results demonstrated that AD-1 reduced the injury, extracellular matrix (ECM) buildup and α-smooth muscle actin (α-SMA) protein expression levels of L929 induced by LPS. Oral administration of AD-1 downregulated the expression of interleukins (such as IL-1β, IL-6 and IL-18), increased the expression of superoxide dismutase (SOD) and glutathione (GSH), reduced the lung coefficient and the content of hydroxyproline (HYP), and mediated the Bax/Bcl-2 protein ratio and P-p53, β-catenin and SIRT3 expression in the lung tissue of mice. Furthermore, AD-1 inhibited the expression levels of TGF-β1, TIMP-1 and α-SMA and reduced inflammatory cell infiltration and collagen deposition in the lung tissue of PF mice. These results indicated that AD-1 could alleviate PF both in vitro and in vivo, and the underlying mechanism may be related to the decrease in ECM deposition and inflammation, the enhancement of antioxidant capacity, and the mediation of lung cell apoptosis and the TGF-β1/TIMP-1/α-SMA signaling pathway, which provide a theoretical basis for the rehabilitation treatment of PF.
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Affiliation(s)
- Tao Li
- Shenyang Pharmaceutical University, Shenyang 110016, China. .,Key Laboratory of Nature Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, P.R. China.
| | - Yu Chen
- Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Yuan Li
- Shenyang Pharmaceutical University, Shenyang 110016, China. .,Basic medical teaching and Research Department, Liaoning Vocational College of Medicine, Shenyang 110101, China
| | - Gang Chen
- Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Yuqing Zhao
- Key Laboratory of Nature Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, P.R. China.
| | - Guangyue Su
- Shenyang Pharmaceutical University, Shenyang 110016, China.
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Inhibition of MACC1-Induced Metastasis in Esophageal and Gastric Adenocarcinomas. Cancers (Basel) 2022; 14:cancers14071773. [PMID: 35406545 PMCID: PMC8997092 DOI: 10.3390/cancers14071773] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Esophageal and Gastric Adenocarcinomas (AGE/S) are characterized by early metastasis and poor survival. MACC1 (Metastasis Associated in Colon Cancer 1) acts in colon cancer as a metastasis inducer and is linked to reduced survival. In this study, we analyzed the prognostic role of MACC1 in a large AGE/S cohort and the potential of MACC1 inhibition in vitro and in vivo. MACC1 is an independent negative prognostic marker in our cohort. In vitro, migration was enhanced by MACC1 in overexpressing cells. This MACC1-related effect could be inhibited by using selumetinib in vitro. In vivo, MACC1 induced faster and larger metastasis development, which could be inhibited by selumetinib. In conclusion, MACC1 is a strong negative prognostic factor in AGE/S and is a potential target for therapy with selumetinib. Abstract Esophageal and Gastric Adenocarcinomas (AGE/S) are characterized by early metastasis and poor survival. MACC1 (Metastasis Associated in Colon Cancer 1) acts in colon cancer as a metastasis inducer and is linked to reduced survival. This project illuminates the role and potential for the inhibition of MACC1 in AGE/S. Using 266 of 360 TMAs and survival data of AGE/S patients, we confirm the value of MACC1 as an independent negative prognostic marker in AGE/S patients. MACC1 gene expression is correlated with survival and morphological characteristics. In vitro analysis of lentivirally MACC1-manipulated subclones of FLO-1 and OE33 showed enhanced migration induced by MACC1 in both cell line models, which could be inhibited by the MEK1 inhibitor selumetinib. In vivo, the efficacy of selumetinib on tumor growths and metastases of MACC1-overexpressing FLO-1 cells xenografted intrasplenically in NOG mice was tested. Mice with high-MACC1-expressing cells developed faster and larger distant metastases. Treatment with selumetinib led to a significant reduction in metastasis exclusively in the MACC1-positive xenografts. MACC1 is an enhancer of tumor aggressiveness and a predictor of poor survival in AGE/S. This effect can be inhibited by selumetinib.
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Treese C, Hartl K, Pötzsch M, Dahlmann M, von Winterfeld M, Berg E, Hummel M, Timm L, Rau B, Walther W, Daum S, Kobelt D, Stein U. S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus. Cells 2022; 11:cells11061056. [PMID: 35326507 PMCID: PMC8947340 DOI: 10.3390/cells11061056] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 11/26/2022] Open
Abstract
Deregulated Wnt-signaling is a key mechanism driving metastasis in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S). The oncogene S100A4 was identified as a Wnt-signaling target gene and is known to promote metastasis. In this project, we illuminate the role of S100A4 for metastases development and disease prognosis of AGE/S. Five gastric cancer cell lines were assessed for S100A4 expression. Two cell lines with endogenous high S100A4 expression were used for functional phenotyping including analysis of proliferation and migration after stable S100A4 knock-down. The prognostic value of S100A4 was evaluated by analyzing the S100A4 expression of tissue microarrays with samples of 277 patients with AGE/S. S100A4 knock-down induced lower migration in FLO1 and NCI-N87 cells. Treatment with niclosamide in these cells led to partial inhibition of S100A4 and to reduced migration. Patients with high S100A4 expression showed lower 5-year overall and disease-specific survival. In addition, a larger share of patients in the S100A4 high expressing group suffered from metachronous metastasis. This study identifies S100A4 as a negative prognostic marker for patients with AGE/S. The strong correlation between S100A4 expression, metastases development and patient survival might open opportunities to use S100A4 to improve the prognosis of these patients and as a therapeutic target for intervention in this tumor entity.
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Affiliation(s)
- Christoph Treese
- Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; (C.T.); or (K.H.); (M.D.); (W.W.); (D.K.)
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.P.); (L.T.); (S.D.)
- Berlin Institute of Health (BIH), 10115 Berlin, Germany
| | - Kimberly Hartl
- Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; (C.T.); or (K.H.); (M.D.); (W.W.); (D.K.)
- Medical Department, Division of Gastroenterology and Hepatology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 10115 Berlin, Germany
| | - Michelle Pötzsch
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.P.); (L.T.); (S.D.)
| | - Matthias Dahlmann
- Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; (C.T.); or (K.H.); (M.D.); (W.W.); (D.K.)
| | - Moritz von Winterfeld
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.v.W.); (E.B.); (M.H.)
| | - Erika Berg
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.v.W.); (E.B.); (M.H.)
| | - Michael Hummel
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.v.W.); (E.B.); (M.H.)
| | - Lena Timm
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.P.); (L.T.); (S.D.)
| | - Beate Rau
- Department of Surgery, Campus Virchow-Klinikum and Campus Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany;
| | - Wolfgang Walther
- Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; (C.T.); or (K.H.); (M.D.); (W.W.); (D.K.)
| | - Severin Daum
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany; (M.P.); (L.T.); (S.D.)
| | - Dennis Kobelt
- Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; (C.T.); or (K.H.); (M.D.); (W.W.); (D.K.)
- German Cancer Consortium (DKTK), 69126 Heidelberg, Germany
| | - Ulrike Stein
- Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; (C.T.); or (K.H.); (M.D.); (W.W.); (D.K.)
- German Cancer Consortium (DKTK), 69126 Heidelberg, Germany
- Correspondence:
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Mranda GM, Xue Y, Zhou XG, Yu W, Wei T, Xiang ZP, Liu JJ, Ding YL. Revisiting the 8th AJCC system for gastric cancer: A review on validations, nomograms, lymph nodes impact, and proposed modifications. Ann Med Surg (Lond) 2022; 75:103411. [PMID: 35386808 PMCID: PMC8977912 DOI: 10.1016/j.amsu.2022.103411] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 02/23/2022] [Indexed: 12/20/2022] Open
Abstract
Gastric cancer is the fifth most frequently diagnosed cancer worldwide, behind breast, lung, colorectal, and prostate cancers. In gastric cancer, multimodality treatment shows prospective benefits and also improves survival. Surgery, however, is the mainstay of curative treatment. The staging of gastric cancer patients is critical for harmonization of care. Accurate stages assure that informed clinical decisions are timely made. The American Joint Committee on Cancer (AJCC) staging system is the most widely applied system in to determine the disease's prognosis and survival prediction. The recently adopted 8th AJCC TNM staging system has been revised to enhance its survival predictive power. Subsequent studies have established the validity of the current edition, demonstrating improved stage stratification, discriminatory power, and survival prediction. However, other studies have cast doubt on the superiority of the new edition. Innovations aimed at further improving its prognosis have resulted in developing of novel models. Advances in our understanding of the tumor microenvironment and molecular categorization of cancer have resulted in proposals for their inclusion in TNM staging as potential complementary factors that enhance survival prediction and prognostic assessment ability. The purpose of this study is to conduct a review of the published literature regarding the validity of the 8th AJCC TNM staging system, proposed modifications, and nomograms.
The 8th AJCC is valid in prognostic stratification of gastric cancer, however, revisions are still required. The yPT staging requires some modifications and inclusion of stages that currently don't exist in the 8th AJCC. High lymph nodes count and anatomical localization improve the prediction ability of the current AJCC. Nomograms comprising of individual prognostic factors are crucial to the current AJCC. Molecular markers positively influence survival prediction of gastric cancer.
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Affiliation(s)
- Geofrey Mahiki Mranda
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
- Department of General Surgery, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Ying Xue
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Xing-Guo Zhou
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Wang Yu
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Tian Wei
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Zhi-Ping Xiang
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Jun-Jian Liu
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
| | - Yin-Lu Ding
- Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, China
- Corresponding author. Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Street, Jinan, 250012, Shandong Province, China.
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Mei Y, Feng X, Feng T, Yan M, Zhu Z, Li T, Zhu Z. Adjuvant Chemotherapy in pT2N0M0 Gastric Cancer: Findings From a Retrospective Study. Front Pharmacol 2022; 13:845261. [PMID: 35250596 PMCID: PMC8891981 DOI: 10.3389/fphar.2022.845261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 02/04/2022] [Indexed: 11/13/2022] Open
Abstract
Background: There is no global consensus on adjuvant chemotherapy (ACT) for pT2N0M0 gastric cancer. We conducted a retrospective study to reveal the role of ACT in such patients. Methods: Patients with pT2N0M0 gastric cancer who underwent radical resection with D2 lymphadenectomy for primary gastric cancer between January 2012 and May 2016 were included. Kaplan-Meier and Cox regression were used to evaluate overall survival (OS), disease-specific survival (DSS) and predictors of prognosis. Stratified analysis based on high-risk factors was conducted. Results: Of enrolled 307 patients, 111 patients underwent surgery alone and 196 patients received ACT. Surgery alone (HR = 2.913, 95% CI: 1.494-5.682, p = 0.002) and total gastrectomy (HR = 2.445, 95% CI: 1.279-4.675, p = 0.007) were independently associated with decreased OS. With the median follow-up of 73.1 months, the 5-year OS rate was 87.9% and 5-year DSS rate was 91.8%. Patients receiving ACT showed a better 5-year OS rate (92.9 vs. 79.3%, p < 0.001) and DSS rate (96.8 vs. 83.0%, p < 0.001) than patients underwent surgery alone. Patients receiving monotherapy (n = 130) had a relatively poor prognosis compared to patients receiving dual-drug (n = 66) without a significant difference (92.3 vs. 93.9%, p = 0.637). In patients without high-risk factors based on the Chinese Society of Clinical Oncology (CSCO) Guidelines, ACT also provided survival benefit (96.0 vs 82.9%, p = 0.038). Conclusions: ACT was accompanied with higher 5-year OS and DSS rates of patients with pT2N0M0 gastric cancer. Patients with pT2N0M0 gastric cancer, regardless of high-risk factors based on the CSCO guidelines, might be considered candidates for ACT. In regard to the therapy regimen, monotherapy might be the optimal choice, considering the adverse events.
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Affiliation(s)
- Yu Mei
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xijia Feng
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tienan Feng
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Yan
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenggang Zhu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Zhenglun Zhu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Hao D, Li Q, Feng QX, Qi L, Liu XS, Arefan D, Zhang YD, Wu S. Identifying Prognostic Markers From Clinical, Radiomics, and Deep Learning Imaging Features for Gastric Cancer Survival Prediction. Front Oncol 2022; 11:725889. [PMID: 35186707 PMCID: PMC8847133 DOI: 10.3389/fonc.2021.725889] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 12/23/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Gastric cancer is one of the leading causes of cancer death in the world. Improving gastric cancer survival prediction can enhance patient prognostication and treatment planning. METHODS In this study, we performed gastric cancer survival prediction using machine learning and multi-modal data of 1061 patients, including 743 for model learning and 318 independent patients for evaluation. A Cox proportional-hazard model was trained to integrate clinical variables and CT imaging features (extracted by radiomics and deep learning) for overall and progression-free survival prediction. We further analyzed the prediction effects of clinical, radiomics, and deep learning features. Concordance index (c-index) was used as the model performance metric, and the predictive effects of multi-modal features were measured by hazard ratios (HRs) at pre- and post-operative settings. RESULTS Among 318 patients in the independent testing group, the hazard predicted by Cox from multi-modal features is associated with their survival. The highest c-index was 0.783 (95% CI, 0.782-0.783) and 0.770 (95% CI, 0.769-0.771) for overall and progression-free survival prediction, respectively. The post-operative variables are significantly (p<0.001) more predictive than the pre-operative variables. Pathological tumor stage (HR=1.336 [overall survival]/1.768 [progression-free survival], p<0.005), pathological lymph node stage (HR=1.665/1.433, p<0.005), carcinoembryonic antigen (CEA) (HR=1.632/1.522, p=0.02), chemotherapy treatment (HR=0.254/0.287, p<0.005), radiomics signature [HR=1.540/1.310, p<0.005], and deep learning signature [HR=1.950/1.420, p<0.005]) are significant survival predictors. CONCLUSION Our study showed that CT radiomics and deep learning imaging features are significant pre-operative predictors, providing additional prognostic information to the pathological staging markers. Lower CEA levels and chemotherapy treatments also increase survival chances. These findings can enhance gastric cancer patient prognostication and inform treatment planning.
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Affiliation(s)
- Degan Hao
- Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, United States
| | - Qiong Li
- Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Qiu-Xia Feng
- Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Liang Qi
- Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xi-Sheng Liu
- Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Dooman Arefan
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Yu-Dong Zhang
- Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Shandong Wu
- Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States
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30
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Zheng H, Zhu W, Niu Z, Li H, Zheng Y, Liu Z, Yao J, Lou H, Hu H, Gong L, Pan H, Pan Q. A Novel Nutrition-Based Nomogram to Predict Prognosis After Curative Resection of Gastric Cancer. Front Nutr 2021; 8:664620. [PMID: 34760907 PMCID: PMC8572887 DOI: 10.3389/fnut.2021.664620] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 09/27/2021] [Indexed: 12/14/2022] Open
Abstract
Objective: We sought to investigate the prognostic significance of body composition and weight change during the first 6 months of adjuvant chemotherapy after R0 resection and develop novel nomograms to accurately predict relapse-free survival (RFS) and overall survival (OS). Methods: This retrospective study included 190 patients who underwent curative radical gastrectomy for gastric cancer and received adjuvant chemotherapy. The changes in weight and body composition including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed for 6 months. LASSO Cox regression and multivariate Cox regression were conducted to evaluate other clinical characteristics, which were used to construct a nomogram for the prediction of 3- and 5-year RFS and OS. The constructed nomogram was subjected to 1,000 resamples bootstrap for internal validation. The Concordance index (C-index) and time-dependent receiver operating characteristic (t-ROC) curves were used to evaluate and compare the discriminative abilities of the new nomograms, non-nutritional nomograms, and pTNM stage. Results: The median follow-up duration was 42.0 (25.2–55.1) months. Factors included in the newly-built nomogram for RFS were pT stage, pN stage, tumor site, tumor size, nerve invasion or not, surgery type, and change of L3SMI, while factors included in the nomogram for OS were pT stage, pN stage, tumor size, nerve invasion or not, surgery type, and change of L3SMI. The C-index and t-ROC indicated that our newly-built nomograms had greater potential to accurately predict prognosis than the non-nutritional nomograms and pTNM stage system. Besides, oral nutritional supplements can reduce the degree of weight and L3SMI loss. Conclusion: Change in skeletal muscle mass during adjuvant chemotherapy can be incorporated into predictive prognostic nomograms for RFS and OS in GC patients after radical resection. Dynamic changes in body composition and weight during adjuvant chemotherapy contribute to the early detection of poor outcomes.
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Affiliation(s)
- Hui Zheng
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Wenchao Zhu
- Department of Radiology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Zhongfeng Niu
- Department of Radiology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Hongsen Li
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Yu Zheng
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Zhen Liu
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Junlin Yao
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Haizhou Lou
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Hong Hu
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Liu Gong
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Hongming Pan
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Qin Pan
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
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Jiang L, Chen Y, Min G, Wang J, Chen W, Wang H, Wang X, Yao N. Bcl2-associated athanogene 4 promotes the invasion and metastasis of gastric cancer cells by activating the PI3K/AKT/NF-κB/ZEB1 axis. Cancer Lett 2021; 520:409-421. [PMID: 34419501 DOI: 10.1016/j.canlet.2021.08.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 08/14/2021] [Accepted: 08/17/2021] [Indexed: 12/25/2022]
Abstract
Bcl2-associated athanogene 4 (BAG4) has been found to be aberrantly expressed in several types of human cancers. However, little is known about its expression, role, and clinical significance in gastric cancer (GC). In this study, we aimed to address these issues and to explore the underlying mechanisms. The expression level of BAG4, measured by immunohistochemistry, was significantly higher in GC tissues than in paired normal tissues. Elevated BAG4 expression was positively correlated with T stage, lymph node metastasis, and tumor size of GC and was associated with unfavorable outcomes of the patients. The overexpression of BAG4 promoted the in vitro invasion and in vivo metastasis of GC cells, and opposite results were observed after silencing of BAG4. Silencing of BAG4 significantly reduced the phosphorylation of PI3K, AKT, and p65, whereas overexpression of BAG4 markedly enhanced the phosphorylation of these molecules. At the same time, manipulating BAG4 expression resulted in the corresponding changes in p65 nuclear translocation and ZEB1 expression. Luciferase reporter and chromatin immunoprecipitation assays verified that p65 binds to the promoter of ZEB1 to upregulate its transcription. Our results demonstrate that BAG4 plays an oncogenic role in the invasion and metastasis of GC cells by activating the PI3K/AKT/NF-κB/ZEB1 axis to induce epithelial-mesenchymal transition.
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Affiliation(s)
- Lei Jiang
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
| | - Yan Chen
- Department of Stomatology, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Guangtao Min
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Jun Wang
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Wei Chen
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Hongpeng Wang
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Xiangwen Wang
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Nan Yao
- Sixth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
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Gu L, Zhang Y, Hong J, Xu B, Yang L, Yan K, Zhang J, Chen P, Zheng J, Lin J. Prognostic Value of Pretreatment Overweight/Obesity and Adipose Tissue Distribution in Resectable Gastric Cancer: A Retrospective Cohort Study. Front Oncol 2021; 11:680190. [PMID: 34249721 PMCID: PMC8264507 DOI: 10.3389/fonc.2021.680190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/09/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND This is a study aimed at exploring the relationship between pretreatment overweight/obesity, adipose tissue distribution, and long-term prognosis of gastric cancer. METHODS A total of 607 gastric cancer patients were involved in the retrospective cohort study. Overweight/obese patients were defined as body mass index (BMI) greater than 25 kg/m2, and adipose tissue distribution parameters, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio were measured at the level of the third lumbar vertebra using computerized tomography images within 15 days before the surgery. Multiple Cox regression models were applied to evaluate the association between overweight/obesity and disease-specific survival (DSS) of gastric cancer, and covariates including age, gender, T stage, N stage, and chemotherapy were adjusted. Furthermore, multiple Cox regression models were performed to evaluate the association between adipose tissue distribution parameters and DSS of gastric cancer; except for covariates mentioned above, overweight/obesity was adjusted additionally. RESULTS Overweight/obesity was a predictive factor (HR = 0.61, 95% CI: 0.37-0.99) for the prognosis of gastric cancer. After additionally adjusting for overweight/obesity, high SAT percentage was an independent protective factor (HR = 0.59, 95% CI: 0.36-0.96), while high VAT percentage (HR = 1.68, 95% CI: 1.06-2.68) and high VAT/SAT ratio (HR = 1.99, 95% CI: 1.19-3.34) were independent risk factors for DSS of gastric cancer. Compared with other patients (overweight/obesity with low VAT/SAT ratio group, non-overweight/obesity or high VAT/SAT ratio group), patients in the non-overweight/obesity with high VAT/SAT ratio group had a worse prognosis (HR = 1.89, 95% CI: 1.28-2.77). CONCLUSION These results suggest that overweight/obesity is a predictive factor for the prognosis of gastric cancer. The VAT/SAT ratio could be used as a promising prognostic factor for gastric cancer. Therefore, in preoperative evaluation of gastric cancer patients, attention should be paid not only to BMI but also to adipose tissue distribution.
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Affiliation(s)
- Lihu Gu
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | | | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Binbin Xu
- Department of Nutrition, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | | | - Kun Yan
- Department of Radiology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jingfeng Zhang
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Department of Radiology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Ping Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jianjun Zheng
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Department of Radiology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jie Lin
- Department of Thoracic Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
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Han C, Xu T, Zhang Q, Liu J, Ding Z, Hou X. The New American Joint Committee on Cancer T staging system for stomach: increased complexity without clear improvement in predictive accuracy for endoscopic ultrasound. BMC Gastroenterol 2021; 21:255. [PMID: 34116629 PMCID: PMC8196466 DOI: 10.1186/s12876-020-01558-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The efficacy of endoscopic ultrasound (EUS) for determining the T category of gastric cancer is variable. The aim of this study was to evaluate the superiority of EUS by using the 6th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the new 7th/8th edition. METHODS A retrospective analysis of clinical and EUS imaging features of 348 gastric carcinoma patients who underwent radical resection were retrospectively analyzed. Differences between the 6th and 7th/8th edition T staging systems for preoperative EUS evaluation were compared. RESULTS The accuracy of EUS T staging was 72.4% for the 7th/8th edition and 78.4% for the 6th edition. T3 stage accuracy was significantly worse when the T3 group status was changed. The tumor location, echoendoscope type, and histological type were associated with inaccuracy. We further analyzed the EUS image features for each tumor T stage and found that an indistinctly visible muscularis propria (MP) or with obvious thickening was considered an indicator of lesions involved in the MP with a sensitivity of 81.3%; an MP completely disappeared and accompanied with a serosal layer intact may be a marker that the lesion invaded to the subserosa. We also found that irregularities in the outer edge of the gastric wall were markers of gastric serosal layer penetration with a positive predictive value of 92.2%. CONCLUSIONS The increased complexity of the 7th/8th edition T staging system is accompanied by worsening of the predictive accuracy for EUS as compared to the 6th edition. Furthermore, the tumor location, echoendoscope type, histological type, and EUS image features for each tumor T stage should warrant attention.
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Affiliation(s)
- Chaoqun Han
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Tao Xu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Qin Zhang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Jun Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Zhen Ding
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
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Zhou L, Li SH, Wu Y, Xin L. Establishment of a prognostic model of four genes in gastric cancer based on multiple data sets. Cancer Med 2021; 10:3309-3322. [PMID: 33934516 PMCID: PMC8124107 DOI: 10.1002/cam4.3654] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 01/22/2023] Open
Abstract
Gastric cancer (GC) is a kind of malignancy with a high mortality and recurrence. An effective prediction model based on ideal biomarkers to assess prognosis could benefit patients for optimization of treatment. Bioinformatics has played an increasingly important role in the study of cancer diseases. Therefore, this study started with bioinformatics to establish a reliable prognostic model of gastric cancer. The gene expression data and clinical data of GC tissues and normal tissues were obtained from the Gene Expression Omnibus (GEO), Genotype‐Tissue Expression (GTEx), and The Cancer Genome Atlas (TCGA) profile database. We finally identified a four gene signature and constructed a prognostic model. The results of internal and external validation showed that the model is highly reliable. In addition, we also constructed a nomogram based on the model, which was verified by a calibration curve to show its predicted accuracy. Comprehensive analysis indicated that the four genes in the model are related to the occurrence and development of tumors, perhaps they are potential targets for tumor treatment. Generally, this prognostic model can bring potential benefits to patients with gastric cancer.
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Affiliation(s)
- Liqiang Zhou
- Department of General Surgery, Nanchang University, The Second Affiliated Hospital of Nanchang University, NanChang, JiangXi, 330006, China
| | - Shi H Li
- Department of General Surgery, Nanchang University, The Second Affiliated Hospital of Nanchang University, NanChang, JiangXi, 330006, China
| | - You Wu
- Department of General Surgery, Nanchang University, The Second Affiliated Hospital of Nanchang University, NanChang, JiangXi, 330006, China
| | - Lin Xin
- Department of General Surgery, Nanchang University, The Second Affiliated Hospital of Nanchang University, NanChang, JiangXi, 330006, China
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Kong XX, Li XL, Tian Y, Ye QC, Xu XM, Liu Y, Yang Q, Zhang LN, Mei YX, Wen JH, Xiao Q, Li JS, Ding KF, Li J. The Clinicopathological Characteristics of Alpha-Fetoprotein-Producing Adenocarcinoma of the Gastrointestinal Tract-A Single-Center Retrospective Study. Front Oncol 2021; 11:635537. [PMID: 33996549 PMCID: PMC8118715 DOI: 10.3389/fonc.2021.635537] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 02/17/2021] [Indexed: 12/30/2022] Open
Abstract
Alpha-fetoprotein (AFP)-producing adenocarcinoma from the gastrointestinal tract (APA-GI) is a rare type of highly malignant tumor with a poor prognosis. It may originate from any site along the GI tract with similar clinicopathological characteristics. As limited research had ever described the characteristics of APA-GI, the present article intends to systemically investigate the clinicopathological characteristics of APA-GI from a single center's retrospective study to deepen the understanding of the disease. A total of 177 patients pathologically diagnosed with APA-GI between 2010 and 2017 at the Second Affiliated Hospital of Zhejiang University, School of Medicine, were included. Also, clinical data of 419 gastric cancers and 609 colorectal cancers from The Cancer Genome Atlas database were also extracted. Clinical information of patients from Second Affiliated Hospital of Zhejiang University, School of Medicine, was collected, and a median follow-up of 14.5 months was performed to investigate clinical characteristics of APA-GI. For the pathological characteristics of APA-GI, hematoxylin-eosin sections were reviewed, and immunohistochemistry of AFP was performed. The results showed that the primary tumor could develop through the whole GI tract, including the esophagus (0.6%), stomach (83.1%), duodenum (1.1%), ileum (0.6%), appendix (0.6%), colon (5.1%), and rectum (7.9%). Hepatoid adenocarcinoma is the main pathological feature of APA-GI. AFP expression level in tumor tissue was not strictly associated with serum AFP or hepatoid differentiation. The prognosis of APA-GI was worse than that of common adenocarcinoma of the GI tract and liver metastasis, and high AFP levels suggest poor prognosis in patients with APA-GI. Therefore, the present study was the first research to systemically explore the clinicopathological characteristics of APA-GI. APA-GI occurs through the whole GI tract with a significantly worse prognosis than common adenocarcinoma of GI. APA-GI should be regarded as one kind of disease for its similar clinicopathological characteristics within patients.
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Affiliation(s)
- Xiang-Xing Kong
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Xin-Lin Li
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
- Department of Breast Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Yu Tian
- Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
| | - Qian-Cheng Ye
- Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
| | - Xiao-Ming Xu
- Zhejiang University Cancer Center, Hangzhou, China
- Department of Pathology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yue Liu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Qi Yang
- Zhejiang University Cancer Center, Hangzhou, China
- Department of Pathology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Li-Na Zhang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Yan-Xia Mei
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Ji-Hang Wen
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Qian Xiao
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Jing-Song Li
- Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
- Research Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, China
| | - Ke-Feng Ding
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
| | - Jun Li
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Center, Hangzhou, China
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Gu J, Zhang S, He X, Chen S, Wang Y. High expression of PIG11 correlates with poor prognosis in gastric cancer. Exp Ther Med 2021; 21:249. [PMID: 33603857 PMCID: PMC7851609 DOI: 10.3892/etm.2021.9680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Accepted: 12/01/2020] [Indexed: 11/06/2022] Open
Abstract
P53-induced gene 11 (PIG11) is an early transcription-related target of p53 that is involved in cell apoptosis and tumor development. However, its biological function in gastric cancer (GC) tissues and relationship with the prognosis of patients with GC have remained elusive. In the present retrospective study, 60 fresh and 790 paraffin-embedded samples of GC were obtained from the Affiliated Hospital of Nantong University (Nantong, China) with complete clinical data from all patients. Reverse transcription-quantitative PCR and tissue microarray-immunohistochemical analysis were used to determine the expression of PIG11 in the respective GC tissues. A receiver operating characteristic (ROC) curve was plotted to determine the diagnostic utility of PIG11 expression in GC. Furthermore, three online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan-Meier plotter, were used for bioinformatics analysis of PIG11. PIG11 expression in GC tissues was high, which was positively correlated with invasive depth (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.019), TNM staging (P<0.001) and carcinoembryonic antigen in serum (P<0.001), and negatively associated with the overall survival of patients with GC. The ROC curve analysis suggested that based on PIG11 expression, it was possible to distinguish GC tissues from adjacent normal tissues (P<0.0001) with a sensitivity and specificity of 81.67 and 76.67%, respectively. In addition, Cox logistic regression analysis demonstrated that high PIG11 expression is a novel biomarker for unfavorable prognosis of patients with GC. Furthermore, the results obtained from the GEPIA database indicated that PIG11 expression is correlated with TNF, carcinoembryonic antigen related cell adhesion molecule 5, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha, VEGFA and kinase insert domain receptor. Therefore, PIG11 expression may be associated with the malignancy of GC and may serve as a potential diagnostic and prognostic biomarker for GC.
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Affiliation(s)
- Juan Gu
- Department of Public Health, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu 224005, P.R. China
| | - Shu Zhang
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Xin He
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Sufang Chen
- Department of Medical Imaging and Laboratory, Xiangnan University, Chenzhou, Hunan 423000, P.R. China
| | - Yan Wang
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
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Wang P, Deng J, Sun Z, Wang W, Wang Z, Xu H, Zhou Z, Liang H. Proposal of a novel subclassification of pN3b for improvement the prognostic discrimination ability of gastric cancer patients. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:e20-e26. [PMID: 32713746 DOI: 10.1016/j.ejso.2020.06.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 06/10/2020] [Accepted: 06/17/2020] [Indexed: 12/15/2022]
Abstract
INTRODUCTION In the recent edition of TNM staging system, pN3b gastric cancer were separated into the staging system for better prognosis accuracy. The definition of pN3b contains a large range of metastasis lymph nodes (mLNs). However, few studies have evaluated the prognosis of pN3b patients and it remains unknown whether these patients were reasonably assigned into the same substage. MATERIALS AND METHODS A total of 642 pN3b patients from a multi-institutional cohort in China were included. Disease-specific survival (DSS) was estimated using the Kaplan-Meier method and the Cox proportional hazards regression analysis was used to identify the independent prognostic factors. Restricted cubic spine model was used to specify the association between the continuous variables and the logarithm Hazard ratios (HRs). The optimal cut-off value of mLNs for DSS was identified using the X-tile software. RESULTS The 5-year DSS rate of total pN3b cohort was 15.4%. The smooth curves showed a non-linear association between the mLNs and the logarithm HRs. All pN3b gastric cancer patients were divided into two subclassifications (pN3b1: 16-24 mLNs, pN3b2: ≥25 mLNs). Significant survival difference was observed between two subclassifications (P = 0.048). Additionally, more LNs examined could decrease the death risk of pN3b patients and bring survival benefit only in pN3b1 patients, but not in pN3b2 patients. CONCLUSIONS We proposed a novel subclassification of pN3b patients, which assigned patients into two subclassifications with significant survival difference. Future study should explore the prognosis value based on this novel subclassification in TNM staging system.
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Affiliation(s)
- Pengliang Wang
- Affiliated Cancer Hospital & Institution of Guangzhou Medical University, Guangzhou, 510060, China
| | - Jingyu Deng
- Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Zhe Sun
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
| | - Wei Wang
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Zhenning Wang
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
| | - Huimian Xu
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
| | - Zhiwei Zhou
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
| | - Han Liang
- Affiliated Cancer Hospital & Institution of Guangzhou Medical University, Guangzhou, 510060, China; Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, 300060, China.
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Zheng D, Chen B, Shen Z, Gu L, Wang X, Ma X, Chen P, Mao F, Wang Z. Prognostic factors in stage I gastric cancer: A retrospective analysis. Open Med (Wars) 2020; 15:754-762. [PMID: 33336033 PMCID: PMC7712043 DOI: 10.1515/med-2020-0164] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/27/2020] [Accepted: 07/14/2020] [Indexed: 01/15/2023] Open
Abstract
Purpose The purpose of this research is to investigate the prognostic factors of patients with stage I gastric cancer (GC) and to determine whether adjuvant chemotherapy improves the prognosis for high-risk patients. Methods We performed a retrospective analysis at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences from January 2001 to December 2015. Cox regression and Kaplan-Meier were used to evaluate the relationship between the patients’ clinicopathologic characteristics and prognosis. Results A total of 1,550 patients were eligible for the study. The 5-year disease-free survival (DFS) rate of all enrolled patients was 96.5%. The pT and pN stages were significantly associated with the prognosis. The 5-year DFS rates of the three subgroups (T1N0, T2N0, and T1N1) were 97.8%, 95.7%, and 90.5%, respectively (p < 0.001). In the T1N1 subgroup, patients not undergoing chemotherapy showed a lower 5-year DFS rate compared to those undergoing chemotherapy, although the difference was not statistically significant. Conclusions Both the pT and pN stages were closely associated with the prognosis of patients with stage I GC. We also found that the danger coefficient of the pN stage was higher than that of the pT stage, and that postoperative adjuvant chemotherapy might be a reasonable approach to improve outcomes of high-risk patients, particularly in the T1N1 group.
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Affiliation(s)
- Dingcheng Zheng
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.,Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, Zhejiang, China.,Ningbo Clinical Research Center for Digestive System Tumors, Ningbo, Zhejiang, China
| | - Bangsheng Chen
- Emergency Medical Center, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China
| | - Zefeng Shen
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
| | - Lihu Gu
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Xianfa Wang
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
| | - Xueqiang Ma
- Department of General Surgery, Zhuji People's Hospital, Shaoxing, Zhejiang, China
| | - Ping Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Feiyan Mao
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Zhiyan Wang
- Department of General Surgery, Ningbo Yinzhou No. 2 Hospital, 998 North Qianhe Road, Ningbo, Yinzhou District, Zhejiang, China
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Impact of multisection and immunohistochemistry in lymph node staging of Gastric Carcinoma - Case series. Sci Rep 2020; 10:3271. [PMID: 32094351 PMCID: PMC7040007 DOI: 10.1038/s41598-020-59000-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 01/23/2020] [Indexed: 11/12/2022] Open
Abstract
Gastric carcinoma (GC) locoregional recurrence may occur even in cases where the tumor has been completely resected, possibly due to lymph node (LN) micrometastases. It is estimated that in 10% to 30% of cases, LN micrometastases are not detected by a conventional method for histological assessment of LN metastases with hematoxylin-eosin (HE). A cross-sectional study assessed 51 patients with GC by histological evaluation of the LN micrometastases through LN multi sectioning associated with immunohistochemistry analysis with monoclonal antibodies AE1 and AE3. Total gastrectomy was performed in 51% of patients. The total number of resected LN nodes was 1698, with a mean number of resected LN of 33.3 ± 13.2 per surgical specimen, of which 187 had metastasis. After the application of LN multisection and immunohistochemistry, LN micrometastases were found in 45.1% of the cases. LN staging changed in 29.4%, and tumor staging changed in 23.5% of the cases. In patients initially staged as pN0, LN staging and tumor staging changed, both in 19.2% of the cases. In patients initially staged as pN1 or more, LN staging changed in 40.0% of them, and tumor staging changed in 28.0% of the cases. The accuracy of HE for the histological staging of LN tumoral involvement was 76%, which was considered insufficient for CG patients staging. Investigation of LN micrometastasis through LN multisection and immunohistochemistry should be performed, particularly in cases where the presence of blood and lymphatic vessel invasion has been identified after conventional histological analysis, as well as in patients with advanced GC.
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Zhang J, Zou S, Luo R, Zhu Z, Xu H, Huang B. Proposal of a novel stage grouping of the Eighth Edition of American Joint Committee on Cancer TNM Staging System for Gastric Cancer: results from a retrospective study of 30 years clinical data from a single institute in China. Expert Rev Gastroenterol Hepatol 2020; 14:55-64. [PMID: 31062631 DOI: 10.1080/17474124.2019.1613152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Objectives: To improve the prognostic accuracy of 8th edition of American Joint Committee on Cancer TNM staging system for gastric cancer by reclassifying N3a category.Methods: 1446 patients who underwent R0 surgery for histologically proven gastric cancers with ≥16 lymph nodes retrieved were selected.Results: Significant prognostic difference was observed among patients in N3a category ('7-10' group vs '11-15' group; P = 0.029). We proposed a revised pN category in which patients with '7-10' metastatic lymph nodes were categorized as r-N3a, '11-15' as r-N3b, and '>15' as r-N3c. Prognosis for patients in T2r-N3aM0 was similar to that of patients in T4aN0M0/T3N1M0/T2N2M0/T1r-N3bM0 (P = 0.584), but significantly better than that of patients in T4bN0M0/T4aN1-2M0/T3N2M0/T2r-N3bM0 (P = 0.031). Similarly, prognoses for patients in T3r-N3aM0 and T4ar-N3aM0 were similar to that of patients in T4bN0M0/T4aN1-2M0/T3N2M0/T2r-N3bM0 (P = 0.136; P = 0.193), but significantly better than that of patients in T4bN1-2M0/T4ar-N3bM0/T3r-N3bM0/T1-2r-N3cM0 (P = 0.011; P = 0.017). A revised TNM system was also proposed, in which T2r-N3aM0 was incorporated into stage IIB, T3r-N3aM0 and T4ar-N3aM0 into stage IIIA. The revised TNM system had better homogeneity, discriminatory ability, and monotonicity of gradients than the 8th edition system.Conclusion: Patients with 7-10 metastatic lymph nodes in T2-T4a categories should be considered lower stage in the final TNM stage.
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Affiliation(s)
- Jiale Zhang
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Shihui Zou
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Rui Luo
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Zhi Zhu
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Huimian Xu
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Baojun Huang
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
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Yao L, Yan J, Gan L, Huang S, Cheng F, Fang N. Upregulation of MANCR predicts poor survival in patients with gastric cancer. Oncol Lett 2019; 18:6801-6806. [PMID: 31807188 DOI: 10.3892/ol.2019.11026] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Accepted: 09/24/2019] [Indexed: 12/15/2022] Open
Abstract
A previous study revealed that MANCR (mitotically associated long non-coding RNA) is implicated in breast cancer. The present study investigated the potential role of MANCR in gastric cancer (GC) and revealed that MANCR was upregulated in GC tissues compared with non-cancerous tissues. MANCR expression was not affected by clinical stages and a high MANCR expression level was associated with poor survival time. MicroRNA (miR)-101 was downregulated in cancer tissues compared with non-cancerous tissues and was inversely associated with MANCR expression. MANCR overexpression in GC cell lines in vitro resulted in miR-101 downregulation; however, miR-101 overexpression did not alter MANCR expression. Furthermore, MANCR overexpression promoted, while miR-101 overexpression inhibited GC cell proliferation. In addition, miR-101 overexpression decreased the effect of MANCR overexpression. The results obtained in the present study revealed that MANCR expression was associated with the survival of patients with GC, and MANCR overexpression in vitro may promote GC by downregulating miR-101 and increasing the proliferation of GC cells.
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Affiliation(s)
- Ling Yao
- Department of Gastroenterology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Jinhua Yan
- Department of Hematology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Lihong Gan
- Department of Gastroenterology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Shenan Huang
- Department of Gastroenterology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Fei Cheng
- Department of Gastroenterology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Nian Fang
- Department of Gastroenterology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China
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Tonouchi A, Sugano M, Tokunaga M, Sugita S, Watanabe M, Sato R, Kaito A, Akimoto T, Ochiai A, Kinoshita T, Kuwata T. Extra-perigastric Extranodal Metastasis is a Significant Prognostic Factor in Node-Positive Gastric Cancer. World J Surg 2019; 43:2499-2505. [PMID: 31312947 DOI: 10.1007/s00268-019-05076-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Extranodal metastasis is an isolated tumor nodule without a residual lymph node structure and has been reported as a poor prognostic factor in gastric cancer. The aim of this study is to assess the prognostic value of extranodal metastasis, especially from the viewpoint of its anatomical distribution. METHODS A total of 139 consecutive gastric cancer patients who underwent curative surgery with lymph node metastasis between 2008 and 2009 were included. Clinicopathological features and patient survival outcomes were retrospectively assessed. Patients with extranodal metastasis were subdivided into two groups: perigastric extranodal metastasis, located near the perigastric area (#1-#7 according to the Japanese classification of gastric carcinoma 15th edition), and extra-perigastric extranodal metastasis, located alongside the major vessels (#8-#12). RESULTS Extranodal metastasis was found in 51 patients (37%), and it was more frequent in those with bulky, ≥pT3, and pStage III tumors. All patients with extra-perigastric extranodal metastasis had recurrence, resulting in a 0% 5-year overall survival rate, which was significantly worse than that of patients with perigastric extranodal metastasis (59%), or those without extranodal metastasis (84%; P < 0.001). Multivariable analysis identified the presence of extra-perigastric extranodal metastasis as an independent poor prognostic factor. CONCLUSIONS Extranodal metastasis, especially extra-perigastric extranodal metastasis, was a pivotal poor prognostic factor in node-positive gastric cancer. Recognizing extra-perigastric extranodal metastasis would help provide optimal therapeutic options to these high-risk patients.
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Affiliation(s)
- Akiko Tonouchi
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Masato Sugano
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan
- Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Masanori Tokunaga
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Shizuki Sugita
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Masahiro Watanabe
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Reo Sato
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Akio Kaito
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Tetsuo Akimoto
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Kashiwa, Japan
| | - Atsushi Ochiai
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan
- Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Takahiro Kinoshita
- Department of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan
- Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Takeshi Kuwata
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.
- Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
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Yang ZL, Zhu MH, Han XJ, Liu QW, Long JH, Wang CX. Modified American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Based on the Node Ratio Can Further Improve the Capacity of Prognosis Assessment for Gastric Cancer Patients. Front Oncol 2019; 9:329. [PMID: 31131256 PMCID: PMC6509971 DOI: 10.3389/fonc.2019.00329] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 04/11/2019] [Indexed: 12/23/2022] Open
Abstract
Background and Objectives: Our aim was to investigate whether the modified American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system based on the node ratio can further improve the capacity of prognosis assessment for gastric cancer (GC) patients regardless of the number of lymph nodes examined (eLNs). Methods: A total of 17,187 GC patients in the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a training set of 7,660 GC patients, we built the tumor-node ratio-metastasis (TNrM) staging system, which was then externally validated with a validation set of 9,527 GC patients. Results: For the training set, the C-index value of the TNrM staging system was significantly higher than that of the AJCC 8th TNM staging system to predict survival for GC patients (C-index: 0.688 vs. 0.671, P < 0.001). Moreover, the C-index value of the TNrM staging system was significantly higher than that of the 8th TNM staging system to predict survival for GC patients with ≤15 eLNs (C-index: 0.682 vs. 0.673, P < 0.001), as well as for GC patients with >15 eLNs (C-index: 0.700 vs. 0.694, P < 0.001). Similar results were found in the validation set. Conclusions: The TNrM staging system predicted survival more accurately and discriminatively than the AJCC 8th TNM staging system for GC patients regardless of the number of eLNs.
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Affiliation(s)
- Ze-Long Yang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.,Department of General Surgery, Hainan Hospital of PLA General Hospital, Sanya, China
| | - Ming-Hua Zhu
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xiu-Jing Han
- Clinical Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qiang-Wei Liu
- Anesthesiology and Operation Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jian-Hai Long
- Department of General Surgery, People's Liberation Army No. 520 Hospital, Mianyang, China
| | - Chun-Xi Wang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.,Department of General Surgery, Hainan Hospital of PLA General Hospital, Sanya, China
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Cao LL, Lu J, Li P, Xie JW, Wang JB, Lin JX, Chen QY, Lin M, Tu RH, Zheng CH, Huang CM. Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database. Gastroenterol Res Pract 2019; 2019:6294382. [PMID: 31097961 PMCID: PMC6487090 DOI: 10.1155/2019/6294382] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 12/18/2018] [Accepted: 01/15/2019] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE To investigate the validity of the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer. METHODS The clinicopathologic data of 7371 patients who were diagnosed with gastric cancer and had 16 or more involved lymph nodes (LNs) were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed. RESULTS Stage migration occurred primarily during stage III between the 7th and 8th edition TNM staging systems. Stages IIIB and IIIC in the 7th edition staging system were divided in the 8th edition and had obvious differences in survival rates (both P < 0.001). The 8th edition TNM stages IIIC and IV showed similar survival rates (P = 0.101). The prognosis of patients with T4aN3bM0 was not different from that of patients with TxNxM1 (P = 0.433), while the prognosis of patients with T4bN3bM0 was significantly poorer than that of patients with TxNxM1 (P = 0.008). A revised TNM system with both T4aN3bM0 and T4bN3bM0 incorporated into stage IV was proposed. Multivariable regression analysis showed that the revised TNM system, but not the 7th and 8th editions, was an independent factor for disease-specific survival (DSS) in the third step of the analysis. Further analyses revealed that the revised TNM system had superior discriminatory ability to the 8th edition staging system, which was also an improvement over the 7th edition staging system. CONCLUSION The 8th edition of the AJCC TNM staging system is superior to the 7th edition for predicting the DSS rates of gastric cancer patients. However, for better prognostic stratification, it might be more suitable for T4aN3bM0/T4bN3bM0 to be incorporated into stage IV in the 8th edition TNM staging system.
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Affiliation(s)
- Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian Province, China
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Chen H, Tang Z, Chen L, Li H, Wang X, Liu F, Sun Y. Evaluation of the impact of tumor deposits on prognosis in gastric cancer and a proposal for their incorporation into the AJCC staging system. Eur J Surg Oncol 2018; 44:1990-1996. [DOI: 10.1016/j.ejso.2018.10.062] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 10/16/2018] [Accepted: 10/17/2018] [Indexed: 02/03/2023] Open
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Yu JI, Lim DH, Lee J, Kang WK, Park SH, Park JO, Park YS, Lim HY, Kim ST, Lee SJ, Kim S, Sohn TS, Lee JH, An JY, Choi MG, Bae JM, Yoo H, Kim K. Comparison of the 7th and the 8th AJCC Staging System for Non-metastatic D2-Resected Lymph Node-Positive Gastric Cancer Treated with Different Adjuvant Protocols. Cancer Res Treat 2018; 51:876-885. [PMID: 30282450 PMCID: PMC6639239 DOI: 10.4143/crt.2018.401] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 09/27/2018] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Commission on Cancer (AJCC) staging system for gastric cancer (GC) patients. Materials and Methods A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability. RESULTS In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT. CONCLUSION Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.
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Affiliation(s)
- Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Do Hoon Lim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeeyun Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Ki Kang
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Se Hoon Park
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Oh Park
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Suk Park
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ho Yeong Lim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Tae Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Su Jin Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Sung Sohn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Ho Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Yeong An
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min Gew Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Moon Bae
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Heejin Yoo
- Statistics and Data Center, Samsung Medical Center, Seoul, Korea
| | - Kyunga Kim
- Statistics and Data Center, Samsung Medical Center, Seoul, Korea
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Gu L, Chen M, Khadaroo PA, Ma X, Kong L, Li X, Zhu H, Zhong X, Pan J, Wang X. A Risk-Scoring Model for Predicting Lymph Node Metastasis in Early Gastric Cancer Patients: a Retrospective Study and External Validation. J Gastrointest Surg 2018; 22:1508-1515. [PMID: 29845571 DOI: 10.1007/s11605-018-3816-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 05/14/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND The possibility of lymph node metastasis (LNM) is critical to the assessment of the indication for endoscopic submucosal dissection. Thus, the aim of this study is to identify the risk factors for LNM and construct a risk-scoring model for patients with early gastric cancer to guide treatment. METHODS A retrospective examination of reports and studies carried out January 2000 and December 2014 was conducted. A risk-scoring model for predicting LNM was developed based on the data thus collected. In addition, the model is subject to verification and validation by three institutions. RESULTS Of the 1029 patients, 228 patients (22%) had LNM. Multivariate analysis showed that female, depressed type, undifferentiated type, submucosa, tumor size, and lymphovascular invasion were significantly associated with LNM. An 11-point risk-scoring model was used to predict LNM risk. An area under the receiver operating characteristic (AUROC) of the risk-scoring model was plotted using the development set and the AUROC of the model [0.76 (95% CI 0.73-0.80)] to predict LNM risk. After internal and external validation, the AUROC curve for predicting LNM was 0.77 (95% CI 0.68-0.86), 0.82 (95% CI 0.72-0.91), and 0.82 (95% CI 0.70-0.94), respectively. CONCLUSIONS A risk-scoring model for predicting LNM was developed and validated. It could help with personalized care for patients with EGC.
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Affiliation(s)
- Lihu Gu
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, No.3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China
| | - Manman Chen
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | | | - Xueqiang Ma
- Zhuji People's Hospital, Shaoxing, Zhejiang, China
| | - Liya Kong
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xinlong Li
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, No.3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China
| | - Hepan Zhu
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, No.3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China
| | - Xin Zhong
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, No.3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China
| | - Junhai Pan
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, No.3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China
| | - XianFa Wang
- Department of General Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, No.3, East Qingchun Road, Hangzhou, 310016, Zhejiang, China.
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