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Tian XY, Mu YP. Serum miR-30c serves as potential biomarkers for the diagnosis and prognosis of gastric cancer. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2025:1-9. [PMID: 40338037 DOI: 10.1080/15287394.2025.2495952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2025]
Abstract
Gastric cancer (GC)，the fourth leading cause of cancer-related deaths globally and thus early detection, is considered critical for diagnosis and treatment of this disease. It is well known that measurement of microRNA (miRNA) may serve as diagnostic and prognostic biomarker for GC. The aim of this study was to determine whether miR-30c was present in patients with gastric cancer and to correlate relative expression with patient survival. A total of 162 GC patients and 150 healthy controls were recruited. miR-30c levels were quantified in serum using quantitative real-time PCR(QRT-PCR). The sensitivity and specificity of circulating miR-30c was compared to carbohydrate antigen (CA) CA72-4, CA19-9, and carcinoembryonic antigen (CEA), 3 known markers associated with GC. QRT-PCR demonstrated downregulation of gene expression of miR-30c in GC patients. Downregulation of miR-30c gene expression was significantly correlated with stage of cancer, lymphatic metastasis, and distal metastasis. The sensitivity to detect GC of miR-30c, CA72-4, CA19-9, and CEA in serum of GC was 80%, 43%, 21%, and 42%, respectively, while specificity was 89%, 57%, 30%, and 78% respectively. Kaplan-Meier survival analysis showed that the presence of low gene expression of miR-30c was effective in predicting poor prognosis in GC patients. Our data suggest that circulating serum miR-30c concentrations may serve as a reliable biomarker for GC occurrence. (212words).
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Affiliation(s)
- Xiao-Yan Tian
- Department of Clinical Test Laboratory, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Hohhot, China
| | - Yong-Ping Mu
- Department of Clinical Test Laboratory, Hohhot First Hospital, Hohhot, China
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Zhao Y, Han J, Yang R, Wang S, Zhao X, Wang Z, Lu H. Evaluating the predictive significance of D-dimer in conjunction with CA724 for the postoperative outcomes in gastric cancer: A retrospective cohort analysis. PLoS One 2025; 20:e0320193. [PMID: 40198649 PMCID: PMC11978037 DOI: 10.1371/journal.pone.0320193] [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: 11/25/2024] [Accepted: 02/15/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Gastric cancer represents a highly aggressive form of malignant tumor originating from the epithelial cells lining the gastric mucosa. Despite notable improvements in treatment approaches over the last few years, the associated mortality rate continues to be considerably high. Therefore, there is a pressing requirement for dependable biomarkers that can be utilized to predict and monitor prognosis, as well as to formulate targeted treatment strategies for patient groups at high risk. METHODS We conducted an analysis of data collected from patients who were diagnosed with gastric cancer and underwent radical gastrectomy at Shanxi Cancer Hospital from June 2017 to June 2018, with follow-up data gathered over a five-year duration until 2023. Patient follow-up information was sourced from the hospital's monitoring system. The analysis focused on the variances in effectiveness of D-dimer against different tumor markers through Cox stratification analysis. The tumor marker that exhibited the most pronounced impact was selected to formulate a novel combined indicator. Furthermore, we examined how this combined indicator influences five-year overall survival (OS) outcomes following gastric cancer surgery using Cox multivariate regression analysis. RESULTS The Cox multivariate regression analysis revealed that the effect value of the D_Dimer-CA724 Middle group on the overall survival rate post-surgery for gastric cancer was found to be 1.42 (1.13-1.78), p = 0.003 (<0.05), in comparison with the D_Dimer-CA724 Low group. For the D_Dimer-CA724 High group, the effect value on overall survival after gastric cancer surgery was 2.11 (1.65-2.68), p < 0.001. Additionally, the trend test results indicated a value of 1.46 (1.29-1.64) with p < 0.001, demonstrating statistical significance. When compared to the D_Dimer-CA724 Low group, both the D_Dimer-CA724 Middle and High groups showed markedly poorer prognoses, with increased risks of 42% and 111%, respectively, highlighting a highly significant finding in clinical practice. CONCLUSION The integrated measure of D-dimer and CA724, referred to as D-dimer_CA724, serves as an independent predictor for the postoperative outcomes of gastric cancer, demonstrating superior predictive capability compared to the individual markers. In clinical settings, patients with gastric cancer exhibiting elevated levels of D-dimer_CA724 tend to experience worse prognoses following surgery. This measure holds significant potential for widespread application and promotion within clinical practice.
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Affiliation(s)
- Yuanzheng Zhao
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Jiaqi Han
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Rong Yang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, ChinaNo. 3, Zhigong New Street, Taiyuan City, Shanxi Province, China
| | - Shuqin Wang
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Xinran Zhao
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Ziyuan Wang
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Hongxia Lu
- Department of Gastroenterology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, ChinaNo. 3, Zhigong New Street, Taiyuan City, Shanxi Province, China
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Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [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: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
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Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
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Zheng HL, Zhang LK, Lv CB, Xu BB, Lin JX, Zheng CH, Huang CM, Xie JW. Impact of dynamic changes of tumor marker in neoadjuvant chemotherapy-treated triple-negative gastric cancer patients: a multi-center study. BMC Cancer 2024; 24:1188. [PMID: 39333952 PMCID: PMC11438086 DOI: 10.1186/s12885-024-12937-9] [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: 07/04/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199 < 37U/ml, CEA < 5 µg/ml and CA125 < 35U/ml) before and after neoadjuvant chemotherapy (NACT) remain unclear. METHODS A total of 352 LAGC patients treated with NACT(NLAGC) from two centers were included. Of the 156 were Triple-negative patients. CA72-4 trajectory groupings was defined as longitudinal changes in CA72-4 levels before and after NACT to identify different potential subgroups and to compare recurrence-free survival (RFS) and overall survival (OS) among subgroups. The predictive performance of the nomogram-trajectory was evaluated using the area under the receiver operating characteristic curve(AUC), decision curve analysis, and C-index. RESULTS In the Triple-negative patients, the Stable group had significantly worse 3-year OS than the Normal, Elevated, and Descend groups(3-year OS: 53.9% vs. 77.9% vs. 73.5% vs. 87.7%;P = 0.002). Cox multivariate analysis showed that CA72-4 trajectory groupings (Stable group: HR:3.442, 95%CI[1.574-7.528], P = 0.002) was an independent prognostic risk factor. In addition, the C-index and AUC values based on the nomogram-trajectory were significantly higher than those of ypTNM staging (C-index: 0.788 vs. 0.719,P < 0.001;AUC: 0.800 vs. 0.667,P < 0.001). Furthermore, The survival analysis revealed that the 3-year OS of the Low-Risk group of nomogram scores was significantly better than that of the High-Risk group(3-year OS:84.7% vs. 29.1%). And the Low-Risk group had the lower cumulative risk of recurrence (P < 0.001). CONCLUSION The CA72-4 trajectory groupings were an independent prognostic factor for NLAGC Triple-negative patients. The predictive efficacy of the Nomogram-trajectory was significantly better than the ypTNM.
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Affiliation(s)
- Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ling-Kang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chen-Bin Lv
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China
| | - Bin-Bin Xu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China.
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China.
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
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Zheng CW, Yang YM, Yang H. Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer. World J Gastrointest Oncol 2024; 16:3905-3912. [PMID: 39350984 PMCID: PMC11438769 DOI: 10.4251/wjgo.v16.i9.3905] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/03/2024] [Accepted: 07/09/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Advanced gastric cancer (AGC) remains a challenging malignancy with poor prognosis. The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment. This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response. AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC. METHODS This prospective study enrolled 60 patients with AGC. All patients received oxaliplatin (130 mg/m2, every 3 weeks) and trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) for six cycles. Serum carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4) were measured before and after treatment. T-lymphocyte subsets, including CD3+, CD4+, CD8+, and CD4+ /CD8+ ratios, were also evaluated. The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS After six cycles of treatment, the CEA, CA19-9, and CA72-4 serum levels significantly decreased compared to baseline levels (P < 0.001). The percentages of CD3+ and CD4+ T lymphocytes increased significantly (P < 0.05), whereas the percentage of CD8+ T lymphocytes decreased (P < 0.05). The CD4+/CD8+ ratio also significantly increased after treatment (P < 0.05). Patients with a higher decrease in serum tumor markers (≥ 50% reduction) and a higher increase in CD4+/CD8+ ratio (≥ 1.5-fold) showed better clinical response rates (P < 0.05). CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC. Combination therapy not only has a direct antitumor effect, but also enhances the immune response in patients with AGC. Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.
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Affiliation(s)
- Cheng-Wan Zheng
- Department of Thyroid Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yun-Mo Yang
- Department of Thyroid Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Hui Yang
- Department of Thyroid Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
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Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, Tian X, Guan X, Cen X, Zhao Y. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct Target Ther 2024; 9:132. [PMID: 38763973 PMCID: PMC11102923 DOI: 10.1038/s41392-024-01823-2] [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: 06/05/2023] [Revised: 03/07/2024] [Accepted: 04/02/2024] [Indexed: 05/21/2024] Open
Abstract
Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.
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Affiliation(s)
- Yue Zhou
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lei Tao
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiahao Qiu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jing Xu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xinyu Yang
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yu Zhang
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
- School of Medicine, Tibet University, Lhasa, 850000, China
| | - Xinyu Tian
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xinqi Guan
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiaobo Cen
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
- National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yinglan Zhao
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Pang C, Ma Y, Shi W, Zi M, Chen J, Liang C, Li X, Liu Z, Du Y. Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer. J Gastrointest Surg 2024; 28:694-702. [PMID: 38458911 DOI: 10.1016/j.gassur.2024.02.023] [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: 11/22/2023] [Revised: 02/09/2024] [Accepted: 02/16/2024] [Indexed: 03/10/2024]
Abstract
PURPOSE This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). METHODS A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. RESULTS The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. CONCLUSION The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.
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Affiliation(s)
- Chuhong Pang
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - Yubo Ma
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Wenyi Shi
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China; School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Mengli Zi
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - Jinxia Chen
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - Chen Liang
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - Xiao Li
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Zhuo Liu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
| | - Yian Du
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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Xu Y, Zhang P, Luo Z, Cen G, Zhang S, Zhang Y, Huang C. A predictive nomogram developed and validated for gastric cancer patients with triple-negative tumor markers. Future Oncol 2024; 20:919-934. [PMID: 37920954 DOI: 10.2217/fon-2023-0626] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023] Open
Abstract
Aim: To predict the prognosis of gastric cancer patients with triple-negative tumor markers. Materials & methods: Prognostic factors of the nomogram were identified through univariate and multivariate Cox regression analyses. Calibration and receiver operating characteristic curves were used to assess accuracy. Decision curve analysis and concordance indexes were utilized to compare the nomogram with the pathological tumor, node, metastasis stage. Results: A nomogram incorporating log odds of positive lymph nodes, tumor size and lymphocyte-to-monocyte ratio was constructed. The calibration and receiver operating characteristic curves (area under the curve >0.85) showed high accuracy in predicting overall survival. The concordance indexes (0.832 vs 0.760; p < 0.001) and decision curve analysis demonstrated that the nomogram was superior to the pathological tumor, node, metastasis stage. Conclusion: A prediction and risk stratification nomogram has been developed and validated for gastric cancer patients with triple-negative tumor markers.
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Affiliation(s)
- Yitian Xu
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Pengshan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Zai Luo
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Gang Cen
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Shaopeng Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Yuan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
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Zhang R, Chen X, Chen G, Zhao Z, Wei Y, Zhang F, Lin J, Nie R, Chen Y. Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality. Ann Surg Oncol 2023; 30:8561-8571. [PMID: 37718336 DOI: 10.1245/s10434-023-14194-9] [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: 06/15/2023] [Accepted: 08/07/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND The effect of a single tumor marker on the prognosis of gastric cancer patients is not ideal. This study explored a novel prognostic assessment method for gastric cancer (GC) patients using a combination of three important tumor markers (CEA, CA72-4, and CA19-9). METHOD Data from 1966 GC patients who underwent curative gastrectomy at Sun Yat-Sen University Cancer Center (Guangzhou, China) were included. Hazard ratios (HR) for all factors for overall survival (OS) were analyzed by Cox regression. A nomogram and calibration curve were used to establish the survival prediction model. The prediction accuracy was evaluated with the concordance index (C-index). RESULTS All patients were divided into four groups (C0-C3) according to the number of elevated tumor markers. The 5-year OS rates of the patients in preoperative groups C0-C3 were 83.8% (81.3-86.4%), 72.8% (68.5-77.4%), 58.9% (50.4-68.9%), and 18.5% (4.0-33.0%), respectively, and those in postoperative groups C0-C3 were 82.1% (79.4-84.8%), 76.1% (72.2-80.3%), 57.6% (48.4-68.5%), and 16.8% (5.1-28.5%), respectively, with significant differences between each C0-C3 subgroup in both preoperative and postoperative cohorts. Multivariate analysis showed that preoperative (HR: 6.001, 95% CI: 3.523-10.221) and postoperative (HR: 8.149, 95% CI: 4.962-13.528) elevated tumor markers were independent risk factors for GC patients. The C-index for the combined use of tumor markers was 0.65-0.66, which was higher than that for using a single tumor marker (0.53-0.56). CONCLUSION The combined use of tumor markers significantly improved the prognostic value compared with using a single tumor marker. The survival prediction model including the combined tumor markers was accurate and effective.
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Affiliation(s)
- Ruopeng Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Xiaojiang Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Guoming Chen
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhoukai Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yicheng Wei
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Feiyang Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jun Lin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Runcong Nie
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
| | - Yingbo Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
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Saeed MK, Al-Ofairi BA, Hassan MA, Al-Jahrani MA, Abdulkareem AM. The clinical significance of some serum tumor markers among chronic patients with Helicobacter pylori infections in Ibb Governorate, Yemen. Infect Agent Cancer 2023; 18:60. [PMID: 37828556 PMCID: PMC10571253 DOI: 10.1186/s13027-023-00542-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 10/02/2023] [Indexed: 10/14/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a carcinogenic bacterium, it is the greatest risk factor for gastric cancer (GC), according to these evidences, there may be a certain association between chronic H. pylori infections and serum levels of tumor markers. This study was conducted to determine serum levels of some tumor markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and cancer antigen 72-4 (CA72-4) in patients with chronic H. pylori infections and evaluate the association between serum tumor marker levels and chronic patients with H. pylori infections in Ibb Governorate, Yemen. SUBJECTS AND METHODS This study involved 200 patients who had been diagnosed with H. pylori infections using a serum immunochromatography antibody test. Stool and blood samples were collected from all patients to confirm the presence of H. pylori through detection of serum H. pylori IgG antibody and stool antigen test (SAT). Additionally, serum samples were analyzed to measurement the level of certain tumor markers CEA, CA19-9 and CA72-4. These tests were conducted at various Hospitals, Gastroenterology and Hepatology clinics in Ibb governorate, Yemen from October 2019 to November 2020. RESULTS The findings of current study showed that the prevalence of H. pylori infections by rapid anti H. pylori test were 200 (100%), 157 (78.5%) by serum H. pylori IgG antibody and 108 (54%) by SAT. In addition, the results showed that 42 (21%) of the patients had abnormal level of CEA, 30 (15%) had abnormal level of CA19-9 and 31 (15.5%) had abnormal level of CA72-4. Most importantly, the results indicated that the serum tumor marker levels CEA, CA19-9 and CA72-4 were correlated with the levels of serum H. pylori IgG antibody as well as positive results from the SAT (P < 0.05). Furthermore, the results indicated that serum tumor marker levels were associated with different infection status. Finally, the results indicated that the serum levels of tumor markers were associated with older ages, symptomatic patients and long duration of H. pylori infections (P < 0.05). CONCLUSION The findings of this study indicated that there is a significant association between chronic H. pylori infections and the serum levels of tumor markers (CEA, CA19-9 and CA72-4). This suggests that the patients with active chronic H. pylori infection may have an increased risk of developing GC. Therefore, monitoring and early detection of H. pylori infection and tumor markers levels in these patients may be crucial for identifying individuals at higher risk and implementing appropriate interventions.
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Affiliation(s)
- Marwan K Saeed
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen.
- Department of Medical Laboratories, University of Science and Technology, Ibb, Yemen.
| | - B A Al-Ofairi
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen
- Departement of Medical Laboratory, Faculty of Medical Sciences, Queen Arwa University, Sana'a, Yemen
| | - Mohammed A Hassan
- Pathology Department, Faculty of Medicine, Taiz University, Taiz, Yemen
| | - M A Al-Jahrani
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen
| | - Ahmed M Abdulkareem
- Department of Biological Sciences, Microbiology Section, Faculty of Science, Sana'a University, Sana'a, Yemen
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Bratei AA, Stefan-van Staden RI, Ilie-Mihai RM, Gheorghe DC. Simultaneous Assay of CA 72-4, CA 19-9, CEA and CA 125 in Biological Samples Using Needle Three-Dimensional Stochastic Microsensors. SENSORS (BASEL, SWITZERLAND) 2023; 23:8046. [PMID: 37836876 PMCID: PMC10575467 DOI: 10.3390/s23198046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/12/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023]
Abstract
Two-needle 3D stochastic microsensors based on boron- and nitrogen-decorated gra-phenes, modified with N-(2-mercapto-1H-benzo[d]imidazole-5-yl), were designed and used for the molecular recognition and quantification of CA 72-4, CA 19-9, CEA and CA 125 biomarkers in biological samples such as whole blood, urine, saliva and tumoral tissue. The NBGr-2 sensor yielded lower limits of determination. For CEA, the LOD was 4.10 × 10-15 s-1 g-1 mL, while for CA72-4, the LOD was 4.00 × 10-11 s-1 U-1 mL. When the NBGr-1 sensor was employed, the best results were obtained for CA12-5 and CA19-9, with values of LODs of 8.37 × 10-14 s-1 U-1 mL and 2.09 × 10-13 s-1 U-1 mL, respectively. High sensitivities were obtained when both sensors were employed. Broad linear concentration ranges favored their determination from very low to higher concentrations in biological samples, ranging from 8.37 × 10-14 to 8.37 × 103 s-1 U-1 mL for CA12-5 when using the NBGr-1 sensor, and from 4.10 × 10-15 to 2.00 × 10-7 s-1 g-1 mL for CEA when using the NBGr-2 sensor. Student's t-test showed that there was no significant difference between the results obtained utilizing the two microsensors for the screening tests, at a 99% confidence level, with the results obtained being lower than the tabulated values.
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Affiliation(s)
- Alexandru-Adrian Bratei
- Laboratory of Electrochemistry and PATLAB, National Institute of Research for Electrochemistry and Condensed Matter, 202 Splaiul Independentei Str., 060021 Bucharest, Romania; (A.-A.B.); (R.-M.I.-M.); (D.-C.G.)
- Faculty of Chemical Engineering and Biotechnologies, National University of Science & Technology Politehnica Bucharest, 060021 Bucharest, Romania
- Department of Pathology, Emergency University Hospital, 050098 Bucharest, Romania
- Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, 540139 Targu Mures, Romania
| | - Raluca-Ioana Stefan-van Staden
- Laboratory of Electrochemistry and PATLAB, National Institute of Research for Electrochemistry and Condensed Matter, 202 Splaiul Independentei Str., 060021 Bucharest, Romania; (A.-A.B.); (R.-M.I.-M.); (D.-C.G.)
- Faculty of Chemical Engineering and Biotechnologies, National University of Science & Technology Politehnica Bucharest, 060021 Bucharest, Romania
| | - Ruxandra-Maria Ilie-Mihai
- Laboratory of Electrochemistry and PATLAB, National Institute of Research for Electrochemistry and Condensed Matter, 202 Splaiul Independentei Str., 060021 Bucharest, Romania; (A.-A.B.); (R.-M.I.-M.); (D.-C.G.)
| | - Damaris-Cristina Gheorghe
- Laboratory of Electrochemistry and PATLAB, National Institute of Research for Electrochemistry and Condensed Matter, 202 Splaiul Independentei Str., 060021 Bucharest, Romania; (A.-A.B.); (R.-M.I.-M.); (D.-C.G.)
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Zhu Q, He P, Zheng C, Chen Z, Qi S, Zhou D, Li Y, Ouyang Q, Zi H, Tang H, Xing J, Xie Y, Zhu S, Ren J, Huang J. Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion. J Cancer Res Clin Oncol 2023; 149:8369-8378. [PMID: 37079049 DOI: 10.1007/s00432-023-04732-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 03/30/2023] [Indexed: 04/21/2023]
Abstract
PURPOSE Early diagnosis is crucial for optimal prognosis of gastric cancer (GC). Hereby, we aimed to identify novel serum autoantibody-based biomarkers for precancerous lesion (PL) and early GC. METHODS We performed serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (Nano-LC-Q-TOF-MS/MS) to screen for GC-associated autoantibodies. The identified autoantibodies were analyzed for potential detection value for PL and GC by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves analysis was conducted to evaluate the accuracy of the biomarkers. RESULTS We identified seven candidates, such as mRNA export factor (RAE1), Nucleophosmin 1 (NPM1), phosphoglycerate kinase 1 (PGK1), and ADP-ribosylation factor 4 (ARF4). Antibodies against all seven proteins were present at higher levels in sera from 242 patients (51 PL, 78 early GC, 113 advanced GC) compared with sera from 122 healthy individuals. RAE1-specific autoantibody discriminated best between patients at different GC stages, with area under the curve (AUC) values of 0.710, 0.745, and 0.804 for PL, early GC, and advanced GC, respectively. Two predictive models composed of gender, RAE1, PGK1, NPM1, and ARF4 autoantibodies (Model 2 for PL) and of age, gender, RAE1, PGK1, and NPM1 autoantibodies (Model 3 for early GC) had improved diagnostic efficiencies, with AUCs of 0.803 and 0.857, sensitivities of 66.7% and 75.6%, and specificities of 78.7% and 87.7%, respectively. CONCLUSION The identified serum tumor-associated autoantibodies (TAAbs) may have good potential for early detection of GC and PL.
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Affiliation(s)
- Qianyu Zhu
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Pingping He
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Cuiling Zheng
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhibin Chen
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Saiping Qi
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Donghu Zhou
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Yanmeng Li
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Qin Ouyang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Huaduan Zi
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Hengcheng Tang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jie Xing
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Yibin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
| | - Jiansong Ren
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jian Huang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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Liu C, Chen C, Peng F, Liang H, Zhong S, Liu T, Li L, Boronin A, Dong W. Determination of serum CA724 levels using fluorescence immunochromatography. BMC Biotechnol 2023; 23:30. [PMID: 37596558 PMCID: PMC10436430 DOI: 10.1186/s12896-023-00801-w] [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: 04/25/2023] [Accepted: 08/08/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND Carbohydrate antigen 724 (CA724) is a sensitive and specific indicator for multiple malignant tumors. The aim of this study was to establish a Eu-time resolved fluorescence immunochromatography (Eu-TRFICO) method for quantitative detection of CA724 in serum. METHODS Eu-TRFICO strips were optimized and assembled. The sensitivity, specificity and precision were evaluated using CA724 standard dilutions and matrix serum. Meanwhile, the reference interval, comparison, and sensitivity/specificity were performed using clinical negative/positive gastric cancer serum samples. RESULTS The standard curve equation was y = 9.869 x - 154.12 (R2 = 0.993), and the sensitivity was 0.42 U/mL. The common interferents in serum could not affect the quantitative results with low cross-reactivities (all no more than 1.09%). All average recoveries of the intra- and interbatch ranged from 102.38 to 106.40%, and all CVs were below 10%. The reference interval of the healthy subjects was < 4.68 U/mL and the reference interval of the subjects with grade I/II gastric cancer was > 9.54 U/mL. Additionally, a high Pearson r (0.9503) and sensitivity/specificity (92.86%/94.20%) were obtained. CONCLUSION This study prepared Eu-TRFICO strips with high sensitivity, specificity, precision and satisfactory clinical testing performance, which provides more options for clinical quantitative and convenient testing of CA724.
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Affiliation(s)
- Chang Liu
- Heilongjiang Academy of Chinese Medicine Sciences, Harbin, 150036, China
| | - Cuicui Chen
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
- Jinan Laide Bio-technology Co., Ltd, Jinan, 271100, China
| | - Fenglan Peng
- Taian Disabled Soldiers' Hospital of Shandong Province, Taian, 271000, China
| | - Huankun Liang
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
| | - Shuhai Zhong
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
| | - Tiancai Liu
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China
| | - Laiqing Li
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
| | - Alexander Boronin
- Laboratory of Plasmid Biology, G.K. Skryabin Institute Of Biochemistry and Physiology of Microorganisms Russian Academy of Sciences, Pushchino, 142290, Russia
| | - Wenqi Dong
- Guangzhou Zhenda Biopharmaceutical Technology Co., Ltd, No. 3 Juquan Road, Huangpu District, Guangzhou, 510663, China.
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Roșu MC, Ardelean A, Moldovan SD, Faur FI, Nesiu A, Totoloci BD. The importance of CA 72-4 and CA 19-9 dosing in gastric cancer. J Med Life 2023; 16:186-188. [PMID: 36937484 PMCID: PMC10015578 DOI: 10.25122/jml-2022-0173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 02/01/2023] [Indexed: 03/21/2023] Open
Abstract
Serological analysis of tumor markers has emerged as a non-invasive method for monitoring cancer patients, including tumor recurrence and response to treatment. Tumor markers have the potential to aid in both the diagnosis and prognosis of cancer, but their most important role currently lies in the monitoring of tumor progression. Tumor markers can also provide valuable information on treatment effectiveness, with changes in plasma values indicating tumor regression or progression. This research aimed to investigate the correlation between the serum detection values of three tumor markers - CEA, CA 19-9, and CA 72-4 - and their utility in the diagnosis and prognosis of patients with gastric cancer. The study seeks to uncover the relationship between these tumor markers and the evolution of gastric cancer, providing insights into their potential use in clinical practice.
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Affiliation(s)
- Mihai Cătălin Roșu
- Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania
- Department of General Surgery, Arad County Emergency University Hospital, Arad, Romania
- Corresponding Author: Mihai Cătălin Roșu, Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania. E-mail:
| | - Andrei Ardelean
- Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania
- Department of General Surgery, Arad County Emergency University Hospital, Arad, Romania
| | - Silviu Daniel Moldovan
- Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania
| | - Flaviu Ionut Faur
- Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania
- 2 General Surgery Clinic, Pius Brinzeu Emergency Clinical Hospital, Timisoara, Romania
| | - Alexandru Nesiu
- Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania
- Department of Urology, Arad County Emergency University Hospital, Arad, Romania
| | - Bogdan Dan Totoloci
- Department of General Surgery, Faculty of Medicine, Vasile Goldiș Western University of Arad, Arad, Romania
- Department of General Surgery, Arad County Emergency University Hospital, Arad, Romania
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The Number of Positive Tumor Markers (NPTM) Achieves Higher Value in the Prognosis Prediction of Gastric Cancer. DISEASE MARKERS 2022; 2022:5145918. [PMID: 36479044 PMCID: PMC9722318 DOI: 10.1155/2022/5145918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 11/04/2022] [Accepted: 11/18/2022] [Indexed: 12/03/2022]
Abstract
Purpose The clinical application of combined tumor markers is still limited. We aim to explore the value of the combination of multiple tumor markers in gastric cancer (GC) prognosis. Methods The prognostic significance was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The estimated area under the curve (AUC) was compared to evaluate the discriminatory ability of different indicators. A nomogram was constructed based on the results of multivariable cox regression, and its performance was evaluated by Harrell's concordance index and calibration curve. Results NPTM (number of positive tumor markers) displayed independent prognostic significance whether in the whole cohort or in patients with different stages. Patients with the all-negative tumor markers had a worse prognosis after postoperative chemotherapy in all cohort (P = 0.023) or in age ≤60 subgroup (P = 0.012), while patients with positive tumor markers had a better prognosis after postoperative chemotherapy in stage III (P = 0.012). The AUC value of NPTM is higher than any individual tumor marker. The 1-, 3-, and 5-year AUC values of the CTNM (combination of NPTM and pTNM) increased by 5%, 4.8%, and 3.6%, respectively, compared with TNM staging system. The nomogram constructed including NPTM showed its high accuracy (C - index = 0.706) versus TNM staging system (C - index = 0.646) and CTNM (C - index = 0.681). Conclusions NPTM was an independent predictor of gastric cancer prognosis, showing more accurate prognostic performance than individual tumor markers. Especially its significance in guiding postoperative adjuvant chemotherapy regimens and predicting prognosis by combination with TNM staging system may have a better clinical application value.
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Yu TH, Wang R, Chen XZ. Multifactorial co-exposure within family of gastric cancer: increased risk of familial gastric cancer and tailored prevention. Med Oncol 2022; 40:19. [PMID: 36414757 DOI: 10.1007/s12032-022-01882-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 11/01/2022] [Indexed: 11/24/2022]
Affiliation(s)
- Tian-Hang Yu
- Gastric Cancer Center and Gastric Cancer Laboratory, West China Hospital, Sichuan University, Chengdu, China
| | - Rui Wang
- Department of Gastroenterology, Nursing Section, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Gastric Cancer Center and Gastric Cancer Laboratory, West China Hospital, Sichuan University, Chengdu, China.
- Department of Gastrointestinal and Hernia Surgery, Second People's Hospital of Yibin City-West China Yibin Hospital, Sichuan University, Yibin, China.
- Cancer Prevention and Control Center of Yibin City, Second People's Hospital of Yibin City-West China Yibin Hospital, Sichuan University, Yibin, China.
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Zhang J, Cui Y, Wei K, Li Z, Li D, Song R, Ren J, Gao X, Yang X. Deep learning predicts resistance to neoadjuvant chemotherapy for locally advanced gastric cancer: a multicenter study. Gastric Cancer 2022; 25:1050-1059. [PMID: 35932353 DOI: 10.1007/s10120-022-01328-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/21/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Accurate pre-treatment prediction of neoadjuvant chemotherapy (NACT) resistance in patients with locally advanced gastric cancer (LAGC) is essential for timely surgeries and optimized treatments. We aim to evaluate the effectiveness of deep learning (DL) on computed tomography (CT) images in predicting NACT resistance in LAGC patients. METHODS A total of 633 LAGC patients receiving NACT from three hospitals were included in this retrospective study. The training and internal validation cohorts were randomly selected from center 1, comprising 242 and 104 patients, respectively. The external validation cohort 1 comprised 128 patients from center 2, and the external validation cohort 2 comprised 159 patients from center 3. First, a DL model was developed using ResNet-50 to predict NACT resistance in LAGC patients, and the gradient-weighted class activation mapping (Grad-CAM) was assessed for visualization. Then, an integrated model was constructed by combing the DL signature and clinical characteristics. Finally, the performance was tested in internal and external validation cohorts using area under the receiver operating characteristic (ROC) curves (AUC). RESULTS The DL model achieved AUCs of 0.808 (95% CI 0.724-0.893), 0.755 (95% CI 0.660-0.850), and 0.752 (95% CI 0.678-0.825) in validation cohorts, respectively, which were higher than those of the clinical model. Furthermore, the integrated model performed significantly better than the clinical model (P < 0.05). CONCLUSIONS A CT-based model using DL showed promising performance for predicting NACT resistance in LAGC patients, which could provide valuable information in terms of individualized treatment.
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Affiliation(s)
- Jiayi Zhang
- Division of Life Sciences and Medicine, School of Biomedical Engineering (Suzhou), University of Science and Technology of China, Suzhou, 215163, Jiangsu, China
- Medical Imaging Department, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, Jiangsu, China
| | - Yanfen Cui
- Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital, Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, 510080, Guangdong, China
| | - Kaikai Wei
- Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, Guangdong, China
| | - Zhenhui Li
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, Yunnan, China
| | - Dandan Li
- Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital, Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China
| | - Ruirui Song
- Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital, Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China
| | | | - Xin Gao
- Division of Life Sciences and Medicine, School of Biomedical Engineering (Suzhou), University of Science and Technology of China, Suzhou, 215163, Jiangsu, China
- Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital, Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China
- Medical Imaging Department, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, Jiangsu, China
| | - Xiaotang Yang
- Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital, Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China.
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Guo GH, Xie YB, Zhang PJ, Jiang T. Blood index panel for gastric cancer detection. World J Gastrointest Surg 2022; 14:1026-1036. [PMID: 36185564 PMCID: PMC9521474 DOI: 10.4240/wjgs.v14.i9.1026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/13/2022] [Accepted: 08/18/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Gastric cancer is a common malignant tumor. Early detection and diagnosis are crucial for the prevention and treatment of gastric cancer.
AIM To develop a blood index panel that may improve the diagnostic value for discriminating gastric cancer and gastric polyps.
METHODS Thirteen tumor-related detection indices, 38 clinical biochemical indices and 10 cytokine indices were examined in 139 gastric cancer patients and 40 gastric polyp patients to build the model. An additional 68 gastric cancer patients and 22 gastric polyp patients were enrolled for validation. After area under the curve evaluation and univariate and multivariate analyses.
RESULTS Five tumor-related detection indices, 12 clinical biochemical indices and 1 cytokine index showed significant differences between the gastric cancer and gastric polyp groups. Carbohydrate antigen (CA) 724, phosphorus (P) and ischemia-modified albumin (IMA) were included in the blood index panel, and the area under the curve (AUC) of the index panel was 0.829 (0.754, 0.905). After validation, the AUC was 0.811 (0.700, 0.923). Compared to the conventional index CA724, the blood index panel showed significantly increased diagnostic value.
CONCLUSION We developed an index model that included CA724, P and IMA to discriminate the gastric cancer and gastric polyp groups, which may be a potential diagnostic method for clinical practice.
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Affiliation(s)
- Guang-Hong Guo
- Department of Laboratory Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Yi-Bin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng-Jun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Tao Jiang
- Medicine Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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Liu C, Chen C, Lai H, Liang H, Zhong S, Guo G, Wang L, Li L. A New Method for Early Screening of Gastric Cancer (G17 and CA724 Dual-Labeled Time-Resolved Fluorescence Immunoassay). COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:1704948. [PMID: 35912162 PMCID: PMC9328981 DOI: 10.1155/2022/1704948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/30/2022] [Accepted: 07/05/2022] [Indexed: 11/18/2022]
Abstract
Gastric carcinoma (GC) is one of the most common malignancies in the world with the great early screening challenges. The study is aimed at establishing a new detection method for early screening GC using time-resolved fluorescence immunoassay (TRFIA) via quantitative detection of gastrin-17 (G-17) and carbohydrate antigen 724 (CA724) in serum. Time-resolved analyzer measured the fluorescence intensity. The standards of G-17/CA724 were used for drawing the standard curve, which is used to calculate the concentration of G-17 and CA724 in serum sample. The sensitivity for G-17 was 0.54 pg/mL and for CA724 was 0.28 U/mL with a wide-range analyze concentration (0.1-1000) pg/mL or U/mL. The average recoveries ranged from 100.52% to 110.30% for G-17 and 103.02% to 116.00% for CA724. All CVs of the intra- and interassay were below 10% with high specificity. There was a high Pearson coefficient between this TRFIA method and the commercially available kits (Pearson r 0.9117 for G-17 and 0.9449 for CA724). Additionally, the cutoff value was 88.41 pg/mL and 5.47 U/mL for CA724 in health subjects. This study established a TRFIA method for simultaneous detection of the concentrations of G-17 and CA724 in serum, which provide a new method for sensitive, accurate, and specific early screening of gastric cancer.
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Affiliation(s)
- Chang Liu
- Heilongjiang Academy of Chinese Medicine Sciences, Harbin, 150036, China
| | - Cuicui Chen
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Hongrui Lai
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Huankun Liang
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Shuhai Zhong
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Guiling Guo
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Lei Wang
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Laiqing Li
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
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Li X, Li S, Zhang Z, Huang D. Association of multiple tumor markers with newly diagnosed gastric cancer patients: a retrospective study. PeerJ 2022; 10:e13488. [PMID: 35611170 PMCID: PMC9124459 DOI: 10.7717/peerj.13488] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 05/03/2022] [Indexed: 01/17/2023] Open
Abstract
Background The purpose of this paper was to explore the correlation between multiple tumor markers and newly diagnosed gastric cancer. Methods We selected 268 newly diagnosed patients with gastric cancer and 209 healthy subjects for correlation research. The detection of multiple tumor markers was based on protein chips and the results were statistically analyzed using SPSS. Results We concluded that gastric cancer was significantly related to gender, age, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and carbohydrate antigen 242 (CA242) positive levels (P < 0.001). After CA199 and CA242 were stratified by gender, the male odds ratio (OR) was 30.400 and 31.242, respectively, while the female OR was 3.424. After CA125 was stratified by age in patients over 54 years old with gastric cancer, the risk of occurrence in the CA125-positive population was 16.673 times that of the CA125-negative patients. Among patients 54 years old and younger, being CA125-positive was not a risk factor for gastric cancer (P = 0.082). AFP, CEA, CA125, CA199, and CA242 positive levels during the M1 stage were statistically significant when compared with the M0 stage and control group (P < 0.001), but the AFP (P = 0.045) and CA125 (P = 0.752) positive levels were not statistically significant when compared with the M0 stage and control group. The combined detection sensitivity of multiple tumor markers was 44.78%. Conclusion Our research shows that gastric cancer is associated with age, gender, and the positive levels of AFP, CEA, CA125, CA199, and CA242. The positive levels of AFP and CA125 were related to the distant metastasis of gastric cancer. To a certain extent, the combined detection sensitivity can be used for the initial screening of gastric cancer.
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Affiliation(s)
- Xiaoyang Li
- Department of Medical Equipment, Sichuan Cancer Hospital, Chengdu, Sichuan, China
| | - Sifeng Li
- Department of Medical, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhenqi Zhang
- Department of Medical Equipment, Sichuan Cancer Hospital, Chengdu, Sichuan, China
| | - Dandan Huang
- Department of Medical Equipment, Sichuan Cancer Hospital, Chengdu, Sichuan, China
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21
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Zhao S, Bi Y, Wang Z, Zhang F, Zhang Y, Xu Y. Accuracy evaluation of combining gastroscopy, multi-slice spiral CT, Her-2, and tumor markers in gastric cancer staging diagnosis. World J Surg Oncol 2022; 20:152. [PMID: 35545785 PMCID: PMC9092869 DOI: 10.1186/s12957-022-02616-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 04/29/2022] [Indexed: 11/10/2022] Open
Abstract
Background To evaluate the diagnostic accuracy of single gastroscopy, multi-slice spiral CT, HER-2 or tumor markers, and their combination in the diagnosis of gastric cancer. Methods A total of 98 patients with gastric cancer were selected as the research subjects. All patients underwent preoperative gastroscopy, MSCT, and the expression levels of HER-2, CEA, CA199, CA724, and CA242 were detected. A control group of 98 normal adults was selected to compare the risk factors for gastric cancer and to analyze the data. Results There was statistical significance in the expression of the 5 markers in tumor size (P < 0.05), but no statistical significance in other clinical data (P > 0.05). The tumor marker CEA in gastric mucosal tissue of patients with gastric cancer had the highest positive detection rate for gastric cancer, and the difference was statistically significant (P < 0.05) compared with gastroscopy, MSCT and other markers. The combined diagnosis had higher sensitivity, specificity and accuracy compared with the single diagnosis of gastric cancer staging, and the difference was statistically significant (P < 0.05). Compared with normal adults, patients with gastric cancer had statistically significant differences in diet, body mass index, and family genetic history (P < 0.05), while there was no statistically significant difference in whether they had type A blood (P > 0.05). Conclusion The combined diagnosis of gastroscopy, MSCT, immunohistochemical marker Her-2, and tumor markers CEA, CA199, CA724, and CA242 can more accurately determine the clinical staging and lesion invasion depth of patients with gastric cancer and can significantly improve the sensitivity of diagnosis.
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Affiliation(s)
- Songbo Zhao
- Department of Radiology, Shengli Oilfield Central Hospital, Dongying, 257034, China
| | - Yangang Bi
- CT Room, Dongying People's Hospital, 317 Dongchengnanyi Road, Dongying, 257091, China
| | - Zhenfang Wang
- CT Room, Dongying People's Hospital, 317 Dongchengnanyi Road, Dongying, 257091, China
| | - Fantao Zhang
- CT Room, Shengli Oilfield Central Hospital, Dongying, 257034, China
| | - Yang Zhang
- CT Room, Dongying People's Hospital, 317 Dongchengnanyi Road, Dongying, 257091, China
| | - Yongyun Xu
- CT Room, Dongying People's Hospital, 317 Dongchengnanyi Road, Dongying, 257091, China.
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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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Shi WQ, Wu SN, Sun T, Shu HY, Yang QC, Li QY, Su T, Pan YC, Liang RB, Shao Y. Risk Factors to Predict Ocular Metastasis in Older Adult Patients With Gastric Cancer:LDL, ApoA1, and CA724. Technol Cancer Res Treat 2022. [PMCID: PMC8733358 DOI: 10.1177/15330338211065876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective: The purpose of this study was to explore the risk factors for Ocular metastasis (OM) of Gastric cancer (GC). Methods: This is a retrospective cohort study. A total of 1165 patients with GC were enrolled in this study and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < .05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC ( P < .001, P = .033, and P = .008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 ( P < .001). Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.
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Affiliation(s)
- Wen-Qing Shi
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
- Jinshan Hospital of Fudan University, Shanghai, China
| | - Shi-Nan Wu
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Tie Sun
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Hui-Ye Shu
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Qi-Chen Yang
- West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Qiu-Yu Li
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Ting Su
- Medical College of Xiamen University, Xiamen, China
- Massachusetts Eye and Ear, Medical School, Boston, MA, USA
| | - Yi-Cong Pan
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Rong-Bin Liang
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Yi Shao
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
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Xiang W, Wang R, Bai D, Yu TH, Chen XZ. Helicobacter Pylori Related Gastric Cancer Screening and Cost-Effectiveness Analysis: A Hospital-Based Cross-Sectional Study (SIGES). Nutr Cancer 2022; 74:2769-2778. [PMID: 35876250 DOI: 10.1080/01635581.2021.2022168] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 11/15/2021] [Accepted: 12/13/2021] [Indexed: 02/08/2023]
Abstract
To evaluate the effectiveness of Helicobacter pylori (Hp) related gastric cancer screening (Hp-GCS) and cost-effectiveness of protocol candidates in a hospital-based cross-sectional study. A total of 163 gastric cancer patients in West China Hospital were retrospectively collected according to ICD-10 code and histologic proof between April 1, 2013 and March 31, 2014, and 15,599 cancer-free controls were simultaneously collected from the health checkup registry. Hp infection was examined by urea breath test (UBT). The prevalence of Hp infection was compared between patients and controls. The diagnostic performance of UBT-based predictive index was tested in both training and validation settings. Cost-effectiveness analysis was conducted to assess candidates of Hp-GCS protocols. The prevalence of Hp infection was 55.8% and 41.2% in gastric cancers and controls, respectively (p < 0.001). UBT-based model showed moderate diagnostic strength in Hp-GCS (AUC = 0.78, 95% CI 0.74-0.82), better than UBT alone (p < 0.001). The sensitivity and specificity of UBT-based index were 80.2% and 61.9% at optimal cutoff in training setting, comparable in validation setting, which sensitivity and specificity were 76.9% and 59.6%. Number needed to screen was decreased along with older age, as well as stronger positivity of UBT. The optimal cost-effective Hp-GCS protocol with detection rate (DR = 77.9%) was endoscopic screening in age 40-59 years and positive UBT, or age ≥60 years without UBT. Incremental analysis suggested a preferable protocol as endoscopic screening in age ≥40 years without UBT (DR = 93.3%). UBT had moderate diagnostic strength in massive gastric cancer screening, and might be cost-effective in middle-aged population (40-59 years). More robust Hp-GCS protocol needs further investigate in test methods and individual biologic features.
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Affiliation(s)
- Wen Xiang
- Department of Gastrointestinal Surgery & Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Rui Wang
- Department of Gastroenterology, Nursing Section, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Bai
- Department of Gastrointestinal Surgery & Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Tian-Hang Yu
- Department of Gastrointestinal Surgery & Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery & Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastrointestinal and Hernia Surgery, the Second People's Hospital of Yibin City, West China Yibin Hospital, Sichuan University, Yibin, China
- Department of General Surgery, the First People's Hospital of Longquanyi District, West China Longquan Hospital, Sichuan University, Chengdu, China
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Wang X, Li J, Liu W, Zhang X, Xue L. The diagnostic value of interleukin 6 as a biomarker for gastric cancer: A meta-analysis and systematic review. Medicine (Baltimore) 2021; 100:e27945. [PMID: 34964773 PMCID: PMC8615365 DOI: 10.1097/md.0000000000027945] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 11/01/2021] [Accepted: 11/01/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Gastric cancer is one of the most common cancers and a main cause of global cancer death. The expression of interleukin 6 is associated with the risk of gastric cancer. But the diagnostic accuracy of interleukin 6 remains unclear. This study was designed to assess the diagnostic performance of interleukin 6 in gastric cancer diagnosis. METHODS The related data was obtained from Oncomine and studied using bioinformatics analysis. The PubMed, Embase, Cochrane Library, Web of science databases were searched for related studies published from inception to July 14, 2020. Measuring tools of diagnostic performance including sensitivity, specificity, and diagnostic odds ratio were pooled using bivariate mixed-effects meta-analysis model. The summery receiver operator characteristic curves were plotted. RESULTS The result from Oncomine showed that the expression of interleukin 6 in gastric cancer (GC) patients was higher than the normal groups (P < .05). Furthermore, a total of 4 eligible articles were enrolled, containing 390 cases and 404 controls. The diagnostic results were as follows: a sensitivity of 0.80 (95% confidence interval [CI] 0.57-0.92), a specificity of 0.86 (95% CI 0.74-0.93), a positive likelihood ratio of 5.76 (95% CI 3.49-9.49), a negative likelihood ratio of 0.23 (95% CI 0.11-0.51) and a diagnostic odds ratio of 24.58 (95% CI 14.14-42.73). The summary area under the receiver operating characteristic curves was 0.90 (95% CI 0.87-0.93). CONCLUSION Higher interleukin 6 expression was detected in GC patients, and interleukin 6 could be a helpful indicator of diagnosis of gastric cancer. Further large-scale prospective studies are required for identifying the diagnostic value of interleukin 6 in gastric cancer.
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Affiliation(s)
- Xiaozi Wang
- Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China
| | - Jie Li
- Department of Hematology, Hebei General Hospital, Shijiazhuang, China
| | - Wenjing Liu
- Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China
| | - Xianghong Zhang
- Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China
| | - Liying Xue
- Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China
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Xu Y, Zhang P, Zhang K, Huang C. The application of CA72-4 in the diagnosis, prognosis, and treatment of gastric cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188634. [PMID: 34656687 DOI: 10.1016/j.bbcan.2021.188634] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 10/09/2021] [Accepted: 10/10/2021] [Indexed: 02/07/2023]
Abstract
The role of conventional serum tumor marker, carbohydrate antigen 72-4 (CA72-4), in assisting diagnosis, monitoring dynamic progression, and evaluating the prognosis of gastric cancer (GC) should not be ignored, especially in the Chinese population. Even though CA72-4 has been used in clinical practice for decades, its modest positivity rate, sensitivity, and specificity did not meet the high demand of the clinical application. However, over the years, some progress in the functions of CA72-4 has been achieved, suggesting that CA72-4 can still be considered a promising marker in oncology. As a biomarker, CA72-4 can achieve improved sensitivity (SEN) and specificity (SPE) when combined with other biomarkers, selecting suitable reference values, improving detection techniques, and identifying the risk threshold. As a predictor, elevated serum CA72-4 levels were found to be significantly associated with prognostic risk factors, further assessing therapeutic validity and resectability. Recently, an effective method to reduce the toxicity of CA72-4 targeted therapy has been developed. Moreover, CA72-4 could induce novel aptamers to react with tumor cells and enhance the efficacy of trastuzumab in HER2-positive GC. Therefore, in this review, we discuss the most recent application of CA72-4 in the diagnosis, prognosis, and treatment of GC.
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Affiliation(s)
- Yitian Xu
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Pengshan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Kundong Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China.
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27
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Xu J, Song J, Wang T, Zhu W, Zuo L, Wu J, Guo J, Yang X. A combination of methylation and protein markers is capable of detecting gastric cancer detection by combined markers. Epigenomics 2021; 13:1557-1570. [PMID: 34632818 DOI: 10.2217/epi-2021-0080] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim: This study aimed to validate a combination of mSEPT9, mRNF180 and CA724 for gastric cancer (GC) detection. Patients & methods: The performance of mSEPT9, mRNF180 and CA724 was examined in a prospective cohort study with 518 participants (151 with GC, 56 with atrophic gastritis, 87 with other gastrointestinal diseases and 224 with no evidence of disease). Results: mSEPT9, mRNF180 or CA724 alone detected 48.3, 37.1 and 43.1% of GC, respectively. The combination of mSEPT9 and mRNF180 detected 60.3% of GC, and the combination of all three markers detected 68.6% of GC. The detection sensitivity of mSEPT9 and mRNF180 was significantly higher for gastric body and in elder subjects. mSEPT9 was correlated with poorer GC survival. Conclusion: The combination of mSEPT9, mRNF180 and CA724 was adequately sensitive for GC detection. The blood mSEPT9 was predictive for GC prognosis.
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Affiliation(s)
- Jianbiao Xu
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Jianlin Song
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Tongmin Wang
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Wenchuan Zhu
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Liangyu Zuo
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Jinzhi Wu
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Jianhui Guo
- Department of General Surgery II, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
| | - Xiaochun Yang
- Department of Ophthalmology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, PR China
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Chen Y, Yang YC, Tang LY, Ge QM, Shi WQ, Su T, Shu HY, Pan YC, Liang RB, Li QY, Shao Y. Risk Factors and Their Diagnostic Values for Ocular Metastases in Gastric Adenocarcinoma. Cancer Manag Res 2021; 13:5835-5843. [PMID: 34326667 PMCID: PMC8315769 DOI: 10.2147/cmar.s311474] [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: 03/17/2021] [Accepted: 05/24/2021] [Indexed: 11/30/2022] Open
Abstract
Objective Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. Methods Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. Results Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001). Conclusion LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.
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Affiliation(s)
- Yue Chen
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China
| | - Yan-Chang Yang
- Department of Anesthesiology, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Li-Ying Tang
- Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People's Republic of China
| | - Qian-Min Ge
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Wen-Qing Shi
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China.,Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Ting Su
- Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People's Republic of China.,Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA
| | - Hui-Ye Shu
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China.,Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Yi-Cong Pan
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China.,Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Rong-Bin Liang
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Qiu-Yu Li
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Yi Shao
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
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Liu Z, Wang Y, Shan F, Ying X, Zhang Y, Li S, Jia Y, Miao R, Xue K, Li Z, Li Z, Ji J. Combination of tumor markers predicts progression and pathological response in patients with locally advanced gastric cancer after neoadjuvant chemotherapy treatment. BMC Gastroenterol 2021; 21:283. [PMID: 34246249 PMCID: PMC8272383 DOI: 10.1186/s12876-021-01785-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/25/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The prognostic values of preoperative tumor markers (TMs) remain elusive in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy treatment (NACT). This study aimed to assess and establish a novel scoring system incorporating carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4) to enhance prognostic accuracy for progression-free survival (PFS) and pathological response (pCR). METHODS Patients' data were retrospectively analyzed from December 2006 to December 2017 in our center. The cutoff value of TMs was determined using the time-dependent receiver operating test characteristics method. These three TMs were allocated 1 point each for the post neoadjuvant chemotherapy combination of tumor markers (post-NACT CTM) scores. The training group comprised 533 patients, responsible for full analysis, and the validation group comprised 137 patients based on the selection protocol. RESULTS Of 533 enrolled patients, 138, 233, 117, and 45 patients scored 0, 1, 2, 3 respectively. The 3-year PFS rate Multivariate analysis revealed that post-NACT CTM score was an independent predictor of PFS (0 vs. 1, HR: 1.34, 95% CI: 0.92-1.96, P = 0.128; 0 vs. 2, HR: 2.03, 95% CI: 1.35-3.05, P = 0.001; 0 vs. 3, HR: 2.98, 95% CI: 1.83-4.86, P < 0.001). The time-dependent area under curve (AUC) revealed a consistent highest level for post-NACT CTM than other three single TMs. Lower post-NACT CTM score significantly correlated with higher pCR rate based on multivariate logistic regression (2/3 vs. 1, OR: 2.77, 95% CI: 0.90-8.53, P = 0.077; 2/3 vs. 0, OR: 4.33, 95% CI: 1.38-13.61, P = 0.012). A nomogram was formed with both internal and external validation. CONCLUSIONS The post-NACT CTM score system served as a strong independent predictor for PFS and pCR in LAGC patients who received NACT. Further population-based studies are required to confirm our results.
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Affiliation(s)
- Zining Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yinkui Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Fei Shan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Xiangji Ying
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Shuangxi Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yongning Jia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Rulin Miao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Kan Xue
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Zhemin Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, 100142, China
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Yin S, Xi R, Wu A, Wang S, Li Y, Wang C, Tang L, Xia Y, Yang D, Li J, Ye B, Yu Y, Wang J, Zhang H, Ren F, Zhang Y, Shen D, Wang L, Ying X, Li Z, Bu Z, Ji X, Gao X, Jia Y, Jia Z, Li N, Li Z, Ji JF, Xi JJ. Patient-derived tumor-like cell clusters for drug testing in cancer therapy. Sci Transl Med 2021; 12:12/549/eaaz1723. [PMID: 32581131 DOI: 10.1126/scitranslmed.aaz1723] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 12/17/2019] [Accepted: 03/17/2020] [Indexed: 02/06/2023]
Abstract
Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical application in precision oncology. PTC tests of 59 patients with gastric, colorectal, or breast cancers revealed an overall accuracy of 93% in predicting their clinical outcomes. We implemented PTC to guide chemotherapy selection for a patient with mucinous rectal adenocarcinoma who experienced recurrence with metastases after conventional therapy. After three cycles of a nonconventional therapy identified by the PTC, the patient showed a positive response. These findings need to be validated in larger clinical trials, but they suggest that the PTC model could be prospectively implemented in clinical decision-making for therapy selection.
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Affiliation(s)
- Shenyi Yin
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Ruibin Xi
- School of Mathematical Sciences, Center for Statistical Science and Department of Biostatistics, Peking University, Beijing 100871, China
| | - Aiwen Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Shu Wang
- Peking University People's Hospital, Beijing 100044, China
| | - Yingjie Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Chaobin Wang
- Peking University People's Hospital, Beijing 100044, China
| | - Lei Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Yuchao Xia
- School of Mathematical Sciences, Center for Statistical Science and Department of Biostatistics, Peking University, Beijing 100871, China
| | - Di Yang
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Juan Li
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Buqing Ye
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Ying Yu
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Junyi Wang
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Hanshuo Zhang
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.,GeneX Health Co. Ltd., Beijing 100195, China
| | - Fei Ren
- Peking University People's Hospital, Beijing 100044, China
| | - Yuanyuan Zhang
- Peking University People's Hospital, Beijing 100044, China
| | - Danhua Shen
- Peking University People's Hospital, Beijing 100044, China
| | - Lin Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Xiangji Ying
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Xiangyu Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Yongning Jia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Ziyu Jia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Nan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China
| | - Jia-Fu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100083, China.
| | - Jianzhong Jeff Xi
- State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
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Xu W, Ma Q, Wang L, He C, Lu S, Ni Z, Hua Z, Zhu Z, Yang Z, Zheng Y, Feng R, Yan C, Li C, Yao X, Chen M, Liu W, Yan M, Zhu Z. Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy. Front Oncol 2021; 11:607640. [PMID: 33937020 PMCID: PMC8082104 DOI: 10.3389/fonc.2021.607640] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 03/19/2021] [Indexed: 01/19/2023] Open
Abstract
Background Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC. Methods A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups. Results Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively. Conclusions We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.
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Affiliation(s)
- Wei Xu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianchen Ma
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lingquan Wang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Changyu He
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Sheng Lu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhentian Ni
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zichen Hua
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenglun Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhongyin Yang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanan Zheng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Runhua Feng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chao Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Li
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuexin Yao
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mingmin Chen
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wentao Liu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Yan
- Department of General 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, 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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Huang C, Hu C, Zhu J, Zhang W, Huang J, Zhu Z. Establishment of Decision Rules and Risk Assessment Model for Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer. Front Oncol 2020; 10:1638. [PMID: 32984033 PMCID: PMC7492596 DOI: 10.3389/fonc.2020.01638] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 07/27/2020] [Indexed: 12/26/2022] Open
Abstract
Background: Preoperative accurate prediction of lymph node status is especially important for the formulation of treatment plans for patients with gastric cancer (GC). The purpose of this study was to establish decision rules and a risk assessment model for lymph node metastasis (LNM) in GC using preoperative indicators. Methods: The clinical data of 554 patients who underwent gastrectomy with D2 lymphadenectomy were collected. A 1:1 propensity score matching (PSM) system was used, and the clinical data of the matched 466 patients were further analyzed. The important risk factors for LNM were extracted by the random forest algorithm, and decision rules and nomogram models for LNM were constructed with a classification tree and the "rms" package of R software, respectively. Results: Tumor size (OR: 2.058; P = 0.000), computed tomography (CT) findings (OR: 1.969; P = 0.001), grade (OR: 0.479; P = 0.000), hemoglobin (Hb) (OR: 1.211; P = 0.005), CEA (OR: 1.111; P = 0.017), and CA19-9 (OR: 1.040; P = 0.033) were independent risk factors for LNM in GC. Tumor size did rank first in the ranking of important factors for LNM in GC and was the first-level segmentation of the two initial branches of the classification tree. The accuracy, sensitivity, specificity, and positive predictive value of the decision rules in diagnosing preoperative LNM in GC were 75.6, 85.7, 73.9, 73.5, and 79.3%, respectively. The accuracy, sensitivity, and specificity of the risk assessment model in predicting preoperative LNM in GC were 79.3, 80.3, and 79.4%, respectively. Conclusion: Tumor size was the most important factor for evaluating LNM in GC. This decision rules and nomogram model constructed to take into account tumor size, CT findings, grade, hemoglobin, CEA, and CA19-9 effectively predicted the incidence of LNM in preoperative GC.
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Affiliation(s)
| | | | | | | | | | - Zhengming Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Chu LY, Peng YH, Yang T, Fang WK, Hong CQ, Huang LS, Xu LY, Li EM, Xu YW, Xie JJ. Circulating Levels of L1-cell Adhesion Molecule as a Serum Biomarker for Early Detection of Gastric Cancer and Esophagogastric Junction Adenocarcinoma. J Cancer 2020; 11:5395-5402. [PMID: 32742486 PMCID: PMC7391208 DOI: 10.7150/jca.41100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 04/21/2020] [Indexed: 02/05/2023] Open
Abstract
Background: Low serum L1 cell adhesion molecule (L1CAM) has been found in several malignant tumors. Here, we aimed to evaluate the diagnostic potential for serum L1CAM in patients with gastric cancers (GC) and esophagogastric junction adenocarcinoma (EJA). Methods: Enzyme-linked immunosorbent assay (ELISA) was carried out to detect L1CAM level in sera of 148 GC patients, 59 EJA patients and 148 healthy controls. Receiver operating characteristics (ROC) was employed to evaluate diagnostic accuracy. Results: The concentrations of serum L1CAM were significantly lower in GC and EJA than those in healthy controls (P<0.001). Detection of L1CAM provided a sensitivity of 83.1%, a specificity of 62.2%, and an area under the curve (AUC) of 0.769 (95% CI: 0.715-0.823) in diagnosing GC, and a sensitivity of 66.1%, a specificity of 62.2%, and an AUC of 0.672 (95% CI: 0.590-0.755) in diagnosing EJA. Similar results were observed in the diagnosis of early-stage GC (0.681 (95%CI: 0.596-0.766)) and early-stage EJA (0.674 (95%CI: 0.528-0.820)). Analysis of clinical data showed that the levels of L1CAM were significantly associated with lymph node metastasis in GC (P<0.05). Conclusions: Our study showed that serum L1CAM might be a diagnostic biomarker for GC and EJA.
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Affiliation(s)
- Ling-Yu Chu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Tian Yang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Wang-Kai Fang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Li-Sheng Huang
- Department of Radiation Oncology, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Li-Yan Xu
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou, China
| | - En-Min Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
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A radiomics-based model for prediction of lymph node metastasis in gastric cancer. Eur J Radiol 2020; 129:109069. [PMID: 32464581 DOI: 10.1016/j.ejrad.2020.109069] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/27/2020] [Accepted: 05/10/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To develop and validate a radiomics-based model for preoperative prediction of lymph node metastasis (LNM) in gastric cancer (GC). METHOD A total of 768 GC patients were enrolled in this retrospective study. Radiomics features were extracted from portal venous phase computed tomography (CT) scans. A radiomics signature was built with highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method in the training cohort (n = 486). The signature was further validated in internal validation (n = 240) and external testing cohorts (n = 42). Multivariate logistic regression analysis was conducted to build a model that combined radiomics signature, serum biomarkers, and lymph node status according to CT. Performance of the model was determined by its discrimination, calibration, and clinical usefulness. The predictive value of the model was also evaluated in early stage GC (EGC) subgroup. RESULTS The radiomics signature comprised 7 robust features showed favorable prediction efficacy in all cohorts. A radiomics-based model that incorporated radiomics signature, serum CA72-4, and CT-reported lymph node status had good calibration and discrimination in training cohort [AUC, 0.92; 95% confidence interval (CI), 0.89-0.95] and validation cohort (AUC 0.86; 95% CI, 0.81-0.91). The model also showed a favorable predictive performance for EGC patients with an AUC of 0.85 (95% CI, 0.76-0.94). Decision curve analysis confirmed the clinical utility of this model. CONCLUSIONS The radiomics-based model showed favorable accuracy for prediction of LNM in GC. The model may also serve as a noninvasive tool for preoperative evaluation of LNM in EGC.
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Kuang J, Gong Y, Xie H, Yan L, Huang S, Gao F, Tang S, Gan J. The prognostic value of preoperative serum CA724 for CEA-normal colorectal cancer patients. PeerJ 2020; 8:e8936. [PMID: 32328348 PMCID: PMC7164426 DOI: 10.7717/peerj.8936] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 03/17/2020] [Indexed: 01/04/2023] Open
Abstract
Background and Purpose There had been no recognized serum tumor marker to predict the prognosis of colorectal cancer (CRC) patients with normal preoperative serum carcinoembryonic antigen (CEA) levels. The purpose of this study was to determine whether preoperative serum carbohydrate antigen 724 (CA724) was of predictive function for the prognosis of CRC patients with normal CEA levels. Methods The medical records of 295 CRC patients with normal CEA levels who underwent surgery at the Department of Colorectal Anal Surgery of the First Affiliated Hospital of Guangxi Medical University (Guangxi, China) between September 2012 and September 2014 were retrospectively reviewed. The Chi-square test was used to test the correlation between preoperative serum CA724 levels and clinical features. Kaplan–Meier curves were conducted to calculate the overall survival (OS) rate and disease-free survival (DFS) of patients. Cox regression analysis was applied to conduct univariate and multivariate analysis of the following four preoperative serum tumor makers namely CA724, carbohydrate antigen 199 (CA199), carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen 242 (CA242) and clinical features. Nomograms for prognostic parameter of OS and DFS were developed using R v3.2.5. Results In the Chi-square test, only pathological node stage (pN stage) (X2 = 14.514, P = 0.001) and differentiation (X2 = 10.712, P = 0.001) were associated with serum CA724 levels. In the Kaplan–Meier analysis, the results revealed that the OS and DFS in patients with high CA724 was poorer than those with normal. In the multivariate Cox regression analysis of OS and DFS, only pT stage, pN stage, metastasis and serum CA724 were independent prognostic risk factors for CRC patients with normal CEA levels. Conclusion Preoperative serum CA724 might serve as a potential prognostic factor for CRC patients with normal serum CEA levels.
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Affiliation(s)
- Jiaan Kuang
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yizhen Gong
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Hailun Xie
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Ling Yan
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Shizhen Huang
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Feng Gao
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Shuangyi Tang
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jialiang Gan
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Zong W, Feng W, Jiang Y, Ju S, Cui M, Jing R. Evaluating the diagnostic and prognostic value of serum long non-coding RNA CTC-497E21.4 in gastric cancer. Clin Chem Lab Med 2020; 57:1063-1072. [PMID: 30763257 DOI: 10.1515/cclm-2018-0929] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 11/26/2018] [Indexed: 12/13/2022]
Abstract
Background Long non-coding RNAs (lncRNAs) have been reported to play a key role in gastric cancer (GC) tumorigenesis. However, the clinical application value of serum lncRNAs in GC has remained largely unknown. We investigated the role of a novel lncRNA named CTC-497E21.4 in the diagnosis and the prognosis of GC. Methods We focused on evaluation of lncRNA CTC-497E21.4 by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). The study involved following aspects: (1) confirmation of the higher lncRNA CTC-497E21.4 expression in different types of GC specimens than corresponding controls; (2) evaluation of monitoring tumor dynamics by the serum lncRNA CTC-497E21.4 assay; (3) evaluation of the prognostic value of lncRNA CTC-497E21.4 assay in GC. Results (1) The method of RTFQ-PCR detection of lncRNA CTC-497E21.4 was evaluated to have high sensitivity and specificity. (2) The expression levels of lncRNA CTC-497E21.4 were higher in GC patients compared with corresponding controls (p<0.001), and the combination of serum lncRNA CTC-497E21.4, CEA and CA19-9 could improve diagnostic sensitivity (96.36%). (3) The serum lncRNA CTC-497E21.4 expression levels were lower in postoperative samples than preoperative samples (p=0.0021) and survival curves downloaded from TCGA showed high lncRNA CTC-497E21.4 levels were associated with poor OS of GC (p=0.0351). Conclusions lncRNA CTC-497E21.4 may be a potential biomarker for the diagnosis and the prognosis of GC.
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Affiliation(s)
- Wei Zong
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, P.R. China
| | - Wei Feng
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, P.R. China
| | - Yun Jiang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, P.R. China
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, P.R. China
| | - Ming Cui
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong 226001, P.R. China
| | - Rongrong Jing
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong 226001, P.R. China
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Wang R, Chen XZ. Prevalence of atrophic gastritis in southwest China and predictive strength of serum gastrin-17: A cross-sectional study (SIGES). Sci Rep 2020; 10:4523. [PMID: 32161305 PMCID: PMC7066171 DOI: 10.1038/s41598-020-61472-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 02/26/2020] [Indexed: 02/06/2023] Open
Abstract
A hospital-based cross-sectional study in SIGES project was conducted during 2016.5-2017.5 in West China Hospital. It was aimed to observe the prevalence of atrophic gastritis (AG) in southwest China, and assess the diagnostic strength of serum gastrin-17 (G-17) in predicting AG in Chinese population. Asymptomatic healthy controls from health check-up, cancer-free patients with unspecific upper gastrointestinal symptoms, and histologically proven gastric cancer patients were eligible, if serum pepsinogen-I (PG-I), PG-II, and G-17 were detected. AG status was classified by the accredited cutoffs of PG-I (<70 ug/L) and PG-I/II ratio (<3). Totally, healthy controls (n = 9,425), symptomatic patients (n = 671) and gastric cancer patients (n = 305) were simultaneously observed, in which the prevalence of AG in southwest China were estimated as 15.9/1,000, 28.3/1,000, and 55.7/1,000 persons, respectively. The age-specific prevalence of AG in healthy controls showed a significantly uphill trend (p for trend <0.001). Higher level of serum G-17 was significantly associated with increased risk of AG in healthy population (15-30 pmol/L, aOR = 20.67, 95% CI 9.17-46.55; >30 pmol/L, aOR = 314.41, 95% CI 166.10-595.12). Throughout the progression of stomach diseases, the diagnostic strength of serum G-17 for AG showed a downhill trend across more advanced situations. In despite of that, serum G-17 displayed a good performance in predicting AG in the entire cross-sectional population (AUC = 0.92, 95% CI 0.89-0.94; SEN = 85.5%; SPE = 93.2%; LR+ = 12.55; LR- = 0.11). Population in southwest China had intermediate prevalence of AG, while the prevalence was increased over age or disease progression. High level of serum G-17 might be a reliable non-invasive measurement to predict AG in southwest Chinese population.
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Affiliation(s)
- Rui Wang
- Department of Gastroenterology, Nursing Section, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery & Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China.
- Department of Gastrointestinal and Hernia Surgery, The Second People's Hosopital of Yibin • West China Yibin Hospital, Sichuan University, Yibin, China.
- Department of General Surgery, The First People's Hospital of Longquanyi • West China Longquan Hospital, Sichuan University, Chengdu, China.
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Wang R, Bai D, Xiang W, Zhang YF, Ba KY, Chen XZ. Helicobacter pylori prevalence in the Southwest of China: A protocol for systematic review. Medicine (Baltimore) 2020; 99:e19369. [PMID: 32176059 PMCID: PMC7220138 DOI: 10.1097/md.0000000000019369] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 01/31/2020] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES This epidemiological research will be aimed to evaluate the longitudinal changes of Helicobacter pylori prevalence in Southwest China during recent period through a systematic review and analysis. METHODS The database PubMed and China National Knowledge Infrastructure will be searched. The cross-sectional studies or cohort studies on either massive or hospital-based health checkup population will be potentially eligible. The study population was originated from one of the southwestern major cities, Chengdu (Sichuan), Chongqing, Kunming (Yunnan), Guiyang (Guizhou), or Lhasa (Tibet). Two reviewers will independently select studies, extract data, and assess the quality of studies. The prevalence of H pylori infection will be estimated. In the individual city, the longitudinal comparisons will be conducted to evaluate the trends referring to the earliest cross-sectional baseline. The risk ratio and its 95% confidence interval will be estimated. Subgroup analyses will be performed in sex-specific and age-specific subsets. Trend analysis for proportions (p for trend) will be estimated in the longitudinal evaluation. If applicable, the longitudinal clearance rate (%) will be estimated. ETHICS AND DISSEMINATION The ethical approval is not required due to the nature of literature-based research. The results will be disseminated through meetings and a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42019120764.
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Affiliation(s)
- Rui Wang
- Nursing Section, Department of Gastroenterology
| | - Dan Bai
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital
| | - Wen Xiang
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital
| | - Yu-Feng Zhang
- Faculty of Clinical Medicine, West China Medical School, Sichuan University, Chengdu
| | - Kun-Yi Ba
- Faculty of Clinical Medicine, West China Medical School, Sichuan University, Chengdu
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital
- Department of Gastrointestinal and Hernia Surgery, The Second People's Hospital of Yibin, West China Yibin Hospital, Sichuan University, Yibin
- Department of General Surgery, The First People's Hospital of Longquanyi, West China Longquan Hospital, Sichuan University, Chengdu, China
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Spatial-Temporal Effects of PM 2.5 on Health Burden: Evidence from China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16234695. [PMID: 31775384 PMCID: PMC6926598 DOI: 10.3390/ijerph16234695] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/20/2019] [Accepted: 11/22/2019] [Indexed: 02/06/2023]
Abstract
By collecting the panel data of 29 regions in China from 2008 to 2017, this study used the spatial Durbin model (SDM) to explore the spatial effect of PM2.5 exposure on the health burden of residents. The most obvious findings to emerge from this study are that: health burden and PM2.5 exposure are not randomly distributed over different regions in China, but have obvious spatial correlation and spatial clustering characteristics. The maximum PM2.5 concentrations have a significant positive effect on outpatient expense and outpatient visits of residents in the current period, and the impact of PM2.5 pollution has a significant temporal lag effect on residents' health burden. PM2.5 exposure has a spatial spillover effect on the health burden of residents, and the PM2.5 concentrations in the surrounding regions or geographically close regions have a positive influence on the health burden in the particular region. The impact of PM2.5 exposure is divided into the direct effect and the indirect effect (the spatial spillover effect), and the spatial spillover effect is greater than that of the direct effect. Therefore, we conclude that PM2.5 exposure has a spatial spillover effect and temporal lag effect on the health burden of residents, and strict regulatory policies are needed to mitigate the health burden caused by air pollution.
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Liu X, Wu Z, Lin E, Li W, Chen Y, Sun X, Zhou Z. Systemic prognostic score and nomogram based on inflammatory, nutritional and tumor markers predict cancer-specific survival in stage II-III gastric cancer patients with adjuvant chemotherapy. Clin Nutr 2019; 38:1853-1860. [PMID: 30075998 DOI: 10.1016/j.clnu.2018.07.015] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 06/29/2018] [Accepted: 07/11/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND To investigate the clinical utility of several established inflammatory, nutritional and tumor markers, and to construct a new scoring system based on preoperative prognostic markers to predict outcomes in gastric cancer (GC). METHODS We retrospectively assessed 688 consecutive patients who underwent curative resection followed by adjuvant chemotherapy for stage II-III GC from 2000 to 2012. RESULTS On multivariate analysis, C-reactive protein/albumin (CRP/Alb) ratio (>0.2), prognostic nutritional index (PNI) (score 1), preoperative body weight loss (>6%) and carbohydrate antigen 19-9 (CA 19-9) (>27 U/mL) independently predicted unfavorable cancer-specific survival (CSS). These 4 preoperative prognostic markers were allocated 1 point each. Then, a new systemic prognostic score (SPS) was constructed based on the total score. Multivariate analysis revealed that SPS was an independent predictor of CSS (P < 0.001). Patients with a SPS of 0, 1, 2, or 3/4 had a 5-year CSS rates of 67.2%, 45.3%, 29.0%, and 10.6%, respectively (0 vs. 1 [P < 0.001], 1 vs. 2 [P = 0.031] and 2 vs. 3/4 [P = 0.004]). The median survival times for SPS 0, SPS 1, SPS 2 and SPS 3/4 were 68.7, 47.1, 28.3 and 16.3 months, respectively. The area under the receiver operating characteristics (ROC) curve for SPS was higher than other markers (P < 0.001). Furthermore, a nomogram that integrated TNM stage, tumor location and SPS exhibited superior discrimination power compared with the TNM stage alone (C-index, 0.714 vs. 0.630, respectively; P < 0.001). CONCLUSION The preoperative SPS combining inflammatory, nutritional and tumor markers independently predicted postoperative survival in stage II-III GC patients treated with adjuvant chemotherapy.
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Affiliation(s)
- Xuechao Liu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Zhiming Wu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Enzi Lin
- Cancer Hospital of Shantou University Medical College, Shantou, 515041, China.
| | - Wei Li
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Yingbo Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Xiaowei Sun
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Zhiwei Zhou
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
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Wang R, Liu K, Chen XZ. Associations between gastric cancer risk and virus infection other than Epstein-Barr virus: The protocol of a systematic review and meta-analysis based on epidemiological studies. Medicine (Baltimore) 2019; 98:e16708. [PMID: 31393376 PMCID: PMC6709195 DOI: 10.1097/md.0000000000016708] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 07/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric cancer is one of the infection associated malignancies. In addition to Helicobacter pylori and Epstein-Barr virus (EBV), other oncoviruses might play potential roles in the development of gastric cancer. Associations of oncoviruses other than EBV with gastric cancer risk are aimed to be comprehensively reviewed and assessed in this systematic review and meta-analysis, to identify any potentially causative oncovirus. It might be informative to identify or deny certain oncoviruses which are candidates of risk factor for gastric cancer. To our knowledge, there is no comprehensive review on oncoviruses other than EBV associated with gastric cancer risk. Positive findings might be helpful to suggest further mechanism investigation and high-risk subpopulation recommendation. METHODS PubMed database will be searched up to Dec 31, 2018. The studies, compared the positivity of any oncovirus other than EBV between cases with histologically proven gastric cancer and healthy or nonmalignant controls, are eligible. The detection of oncovirus either in tissue or blood is acceptable. Selection, quality assessment (Newcastle-Ottawa Scale), and data extraction of eligible studies will be performed by 2 independent reviewers. Pooled prevalence of any oncovirus will be combined by meta-analysis for rate. Pooled odds ratio between gastric cancer cases and controls will be estimated by meta-analysis. Heterogeneity and publication bias will be tested. In sensitivity analysis, the leave-one-out method and exclusion of low power studies will be applied where applicable. RESULTS This review was not submitted for any ethical approval due to the literature-based nature. The results will be published in a journal and presented at conferences for academic purposes.Registration number was CRD42015029703 in the PROSPERO International Prospective Register of Systematic Reviews. CONCLUSIONS To our knowledge, there is no comprehensive review on oncoviruses other than EBV associated with gastric cancer risk. Positive findings might be helpful to suggest further mechanism investigation and high-risk subpopulation recommendation.
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Affiliation(s)
- Rui Wang
- Nursing Section, Department of Gastroenterology
| | - Kai Liu
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China
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Li F, Huang J, Liu J, Xu W, Yuan Z. Multivariate analysis of clinicopathological and prognostic significance of miRNA 106b~25 cluster in gastric cancer. Cancer Cell Int 2019; 19:200. [PMID: 31384175 PMCID: PMC6664745 DOI: 10.1186/s12935-019-0918-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 07/22/2019] [Indexed: 12/11/2022] Open
Abstract
Background miRNA 106b~25 cluster were demonstrated to be an oncogene. In previous study, we had analyzed the diagnostic significance of miRNA 106b~25 based on its carcinogenesis effect. The significance of miRNA 106b~25 for prognosis of gastric cancer were not researched. Methods We applied multivariate analysis of PCA, PLS-DA and Cox Regression for clinicopathological features and survival time to explore the significance of miRNA 106b~25 expression in plasma and cancer tissues for gastric cancer. Results The expression of miRNA 106b, miRNA 93 and miRNA 25 in plasma were positively correlated with their expression in tumor tissues. Via PCA analysis, it was found that miRNA 106b~25 expression in plasma and tumor, T, N and TNM stage were correlated with each other. Via PLS-DA analysis, we identified that T, N and TNM stage were important factors for miRNA 106b~25 expression both in plasma and tumor (all VIP value > 1.2). According to loading weights of variables for the first and second components, it was found that the importance of the miRNA 106b~25s expression carried with the progressed stage of gastric cancer. In the survival analysis, COX regression showed that T stage, plasma miRNA 106b and tumor miRNA 93 were significant risk factors for overall survival [HR: 0.400 (0.205–0.780); P = 0.007; HR: 0.371 (0.142–0.969), P = 0.043; 0.295 (0.134–0.650), P = 0.002]. Conclusion Plasma and tumor miRNA 106b~25 expression correlated with T, N and TNM stage. Increased miRNA 106b~25 expression was important characters carried with gastric cancer progression. T stage, plasma miRNA106b and tumor miRNA 93 significant risk factors for overall survival. Electronic supplementary material The online version of this article (10.1186/s12935-019-0918-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fangxuan Li
- 1Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin, 300060 China.,2Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060 China
| | - Jinchao Huang
- 2Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060 China.,3Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060 China
| | - Juntian Liu
- 2Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060 China
| | - Wengui Xu
- 3Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060 China
| | - Zhiyong Yuan
- 1Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin, 300060 China
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Zhang P, Wang M, Bai L, Zhuang W. A unique case of ectopic pancreas presenting as jejunal malignance. J Surg Case Rep 2019; 2019:rjz217. [PMID: 31308933 PMCID: PMC6622116 DOI: 10.1093/jscr/rjz217] [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: 05/10/2019] [Revised: 06/21/2019] [Accepted: 06/25/2019] [Indexed: 02/05/2023] Open
Abstract
Ectopic pancreas is defined as pancreatic tissues having no anatomic or vascular connections with the orthotopic pancreas. It is difficult for clinicians to diagnose this disease without performing a histopathological examination because it lacks specific clinical manifestations. This case report is of a 46-year-old woman who presented with epigastric pain. She had elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4). Abdominal contrast-enhanced computed tomography (CT) revealed a persistently enhanced mass in the proximal jejunum, which was confirmed as ectopic pancreas via histopathological examination. Her serum CEA and CA72-4 levels were restored to normal ranges after resecting the jejunal ectopic pancreas. This is the first reported case of ectopic pancreas causing an elevation in serum CEA and CA-724 levels; this report supports the metaplasia theory and suggests that jejunal masses should be cautiously diagnosed for avoiding unnecessary concerns among patients and their families.
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Affiliation(s)
- Peng Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Mojin Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Lifen Bai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Wen Zhuang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Sichuan, China
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Bai H, Deng J, Zhang N, Liu H, He W, Liu J, Liang H. Predictive values of multidetector-row computed tomography combined with serum tumor biomarkers in preoperative lymph node metastasis of gastric cancer. Chin J Cancer Res 2019; 31:453-462. [PMID: 31354214 PMCID: PMC6613502 DOI: 10.21147/j.issn.1000-9604.2019.03.07] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 03/08/2019] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVE Multidetector-row computed tomography (MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer (GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC. METHODS The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery. RESULTS With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen (CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis (up to 89.3%) before surgery. CONCLUSIONS MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.
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Affiliation(s)
- Huihui Bai
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jingyu Deng
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Nannan Zhang
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Huifang Liu
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Wenting He
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jinyuan Liu
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Han Liang
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
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Hu PJ, Chen MY, Wu MS, Lin YC, Shih PH, Lai CH, Lin HJ. Clinical Evaluation of CA72-4 for Screening Gastric Cancer in A Healthy Population: A Multicenter Retrospective Study. Cancers (Basel) 2019; 11:cancers11050733. [PMID: 31137895 PMCID: PMC6562516 DOI: 10.3390/cancers11050733] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 05/20/2019] [Accepted: 05/22/2019] [Indexed: 12/11/2022] Open
Abstract
Early detection is important for improving the survival rate of patients with gastric cancer (GC). Serum tumor markers have been widely used for detecting GC. However, their clinical values remain controversial. This study aims to investigate the role of serum cancer antigen 72-4 (CA72-4) in the diagnosis of GC in a healthy population. A total of 7757 adults who underwent upper gastrointestinal endoscopy and serum CA72-4 level measurement in multicenters in Taiwan from January 2006 to August 2016 were recruited in this retrospective study. Risk factors for GC, serum tumor markers, and esophagogastroduodenoscopy (EGD) findings were evaluated. High serum levels of CA72-4 were found in 7.2% of healthy adults. CA72-4 level showed lower sensitivity (33.3%) but higher specificity (92.8%); however, the positive predictive value was quite low (0.18%). After adjustment of clinical risk factors for GC using EGD findings, gastric ulcer (adjusted odds ratio (aOR) = 2.11), gastric polyps (aOR = 1.42), and atrophic gastritis (aOR = 1.27) were significantly associated with high serum CA72-4 levels. Furthermore, both age (OR = 1.01) and Helicobacter pylori infection (OR = 1.44) exhibited a significant association with high serum CA72-4 levels. These results indicate that routine screening of CA72-4 levels for diagnosing GC in asymptomatic patients may be ineffective due to low sensitivity and low positive predictive value. The clinical utility of EGD findings along with serum CA72-4 level for screening healthy individuals with GC is warranted.
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Affiliation(s)
- Ping-Jen Hu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackey Memorial Hospital, Taitung 95054, Taiwan.
| | - Ming-Yao Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang-Ho Hospital, New Taipei 23562, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Ming-Shun Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Division of Gastroenterology, Department of Internal Medicine, Wan-Fang Hospital, 11696 Taipei, Taiwan.
| | - Ying-Chin Lin
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Ping-Hsiao Shih
- Center for Cell Therapy, Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung 40447, Taiwan.
| | - Chih-Ho Lai
- Center for Cell Therapy, Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung 40447, Taiwan.
- Department of Microbiology and Immunology, Molecular Infectious Disease Research Center, Chang Gung University and Chang Gung Memorial Hospital, Linkou 33305, Taiwan.
| | - Hwai-Jeng Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang-Ho Hospital, New Taipei 23562, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
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Wang SL, Yu GY, Yao J, Li ZS, Mao AR, Bai Y. Diagnostic role of carbohydrate antigen 72-4 for gastrointestinal malignancy screening in Chinese patients: A prospective study. J Dig Dis 2018; 19:685-692. [PMID: 30345716 DOI: 10.1111/1751-2980.12681] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 10/16/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Over the past decades, carbohydrate antigen 72-4 (CA72-4) was thought to be a tumor marker that was elevated in healthy individuals and patients with malignancies, including gastrointestinal (GI), ovarian, endometrial and lung malignancies. Furthermore, studies found that elevated serum CA72-4 might predict digestive tumors, especially gastric tumors, although there was still neither a sensitive nor specific tumor biomarker for gastric cancer (GC). This study aimed to evaluate the diagnostic accuracy of CA72-4 in predicting malignancies, especially GC. METHODS Altogether 403 patients underwent a CA72-4 test after admission to the Department of Gastroenterology in Changhai Hospital, the Second Military Medical University, from 1 June 2015 to 31 October 2015. Their age and sex, main symptoms, and final diagnoses were summarized. RESULTS The positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of CA72-4 for diagnosing GC were 31.58%, 79.17%, 1.70, and 0.97, respectively. In the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve for discriminating between patients with GC and those without was 0.62. CONCLUSION Performing a CA72-4 test on its own is of little use for predicting malignances, especially GC, in patients with GI diseases.
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Affiliation(s)
- Shu Ling Wang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Guan Yu Yu
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Jun Yao
- Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Guangdong, China
| | - Zhao Shen Li
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - An Rong Mao
- Department of Hepatic Surgery and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yu Bai
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
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Lin JX, Wang W, Lin JP, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu R, Zheng CH, Huang CM, Zhou ZW, Li P. Preoperative Tumor Markers Independently Predict Survival in Stage III Gastric Cancer Patients: Should We Include Tumor Markers in AJCC Staging? Ann Surg Oncol 2018; 25:2703-2712. [PMID: 29971670 DOI: 10.1245/s10434-018-6634-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Indexed: 12/27/2022]
Abstract
OBJECTIVE The aim of this study was to determine the prognostic significance of preoperative carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels in patients with resectable gastric cancer (GC). PATIENTS AND METHODS Patients who underwent a radical resection for GC at the Fujian Medical University Union Hospital between 2007 and 2014 were included in this study. The estimated area under the curve (AUC) was compared to evaluate the discriminatory ability of tumor makers. Additional external validation was performed using a dataset from Sun Yat-sen University Cancer Center. RESULTS Preoperative CEA/CA19-9 levels were identified as an independent predictor of overall survival (OS) and disease-specific survival (DSS) (both p < 0.05) in the development group. In a subgroup analysis based on TNM stage, preoperative CEA/CA19-9 levels clearly stratified the survival rates for stage III GC (p < 0.05). A multivariate analysis revealed that preoperative CEA/CA19-9 levels were an independent prognostic factor (p < 0.05) in stage III; the AUC of the preoperative CEA/CA19-9 was equivalent to that of T stage. A prediction model (TNMC) for stage III GC was developed by incorporating preoperative CEA/CA19-9 levels into the American Joint Committee on Cancer (AJCC) staging system. The AUC of the TNMC was significantly higher than that of the TNM staging system at 1, 3, and 5 years postoperatively (all p < 0.05), with similar results also being obtained in the external validation set. CONCLUSION Preoperative CEA/CA19-9 levels are an independent predictor of OS and DSS in stage III GC patients. The inclusion of preoperative CEA/CA19-9 levels in AJCC TNM staging provided an optimal prognosis in stage III GC.
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Affiliation(s)
- 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
| | - Wei Wang
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China
| | - Jun-Peng 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - Ruhong 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
| | - 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.
| | - Zhi-Wei Zhou
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 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.
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The Combination of Seven Preoperative Markers for Predicting Patients with Gastric Cancer to Be Either Stage IV or Non-Stage IV. Gastroenterol Res Pract 2018; 2018:3450981. [PMID: 29967637 PMCID: PMC6008646 DOI: 10.1155/2018/3450981] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 05/09/2018] [Accepted: 05/16/2018] [Indexed: 02/06/2023] Open
Abstract
To assess whether preoperative markers could predict the stage of patients with gastric cancer. We analyzed retrospectively the preoperative indicators between stage IV and non-stage IV gastric cancer at the Gastrointestinal Surgery of Nanjing Drum Tower Hospital. A total of 500 patients with gastric cancer were screened. Of all the variables, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, carbohydrate antigen (CA) 199, carbohydrate antigen (CA) 724, carbohydrate antigen (CA) 242, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), blood platelet count (PLT), white blood cell (WBC) count, C-reactive protein (CRP), neutrophil count (NC), lymphocyte count (LC), neutrophil-lymphocyte ratio (NLR), hemoglobin (HB), aspartate aminotransferase (AST), and ascites were found to have statistical differences between the two groups. Then, Stepwise Discriminant Analysis was conducted to establish a prediction model including 7 indexes (CA724, CA242, TT, PLT, CRP, AST, and ascites). According to the model, 90.6% of original grouped cases were correctly classified and 90.6% of cross-validated grouped cases were correctly classified. We built a discriminant including CA724, CA242, TT, PLT, CRP, AST, and ascites for predicting patients with gastric cancer to be either stage IV or non-stage IV. According to this discriminant, 90.6% of patients could be correctly predicted.
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Li J, Xu L, Run ZC, Feng W, Liu W, Zhang PJ, Li Z. Multiple cytokine profiling in serum for early detection of gastric cancer. World J Gastroenterol 2018; 24:2269-2278. [PMID: 29881236 PMCID: PMC5989241 DOI: 10.3748/wjg.v24.i21.2269] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 02/27/2018] [Accepted: 03/18/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the value of multiparameter joint analysis in the early diagnosis of gastric cancer (GC) in clinical practice.
METHODS Concentrations of CEA, CA724 and three kinds of cytokines (TNF-α, IL-6 and IL-8) in 176 GC patients, 117 atypical hyperplasia patients, and 204 healthy control individuals were used for building the diagnostic model, then 58 GC patients, 41 atypical hyperplasia patients, and 66 healthy control individuals were enrolled independently. The joints of the indicators were analyzed by binary logistic regression analysis method.
RESULTS For discriminating the healthy control group and the GC group, IL-6 had the best diagnostic value, and the area under curve (AUC) of joint analysis was 0.95 (0.93-0.97). For the early stage and advanced stage GC, the AUC were 0.95 (0.92-0.98) and 0.95 (0.92-0.97). For discriminating the atypical hyperplasia group and GC group, CA724 had the best diagnostic value, and the AUC of joint analysis was 0.97 (0.95-0.99). For the early stage and advanced stage GC groups, the AUC were 0.98 (0.96-0.99) and 0.96 (0.94-0.98). After evaluation, for discriminating the GC, early stage GC and advanced cancer group from the healthy control group, the diagnostic sensitivity was 89.66%, 84.21% and 92.31%, respectively, and the specificity was 92.42%, 90.91% and 90.91%. For discriminating the GC, early stage GC and advanced cancer groups from the atypical hyperplasia group, the diagnostic sensitivity was 87.93%, 78.95% and 92.31%, respectively, and the specificity was 87.80%, 85.37% and 90.24%.
CONCLUSION We have built a diagnostic model including CEA, CA724, IL-6, IL-8, and TNF-α. It may provide potential assistance as a screening method for the early detection of GC.
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Affiliation(s)
- Jian Li
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Liang Xu
- Department of Oncology, General Hospital of Liaohe Oil Field, Panjin 124010, Liaoning Province, China
| | - Zeng-Ci Run
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Wen Feng
- Department of Pathology, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Wen Liu
- Department of Central Laboratory, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Peng-Jun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhi Li
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
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Kotzev AI, Draganov PV. Carbohydrate Antigen 19-9, Carcinoembryonic Antigen, and Carbohydrate Antigen 72-4 in Gastric Cancer: Is the Old Band Still Playing? Gastrointest Tumors 2018; 5:1-13. [PMID: 30574476 DOI: 10.1159/000488240] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 03/08/2018] [Indexed: 12/12/2022] Open
Abstract
Background Gastric cancer (GC) is characterized by aggressive behavior and a high mortality rate. The diagnosis of GC is challenging because the GC is often diagnosed in an advanced stage. The use of tumor markers is a putative way to improve the detection and treatment in patients with GC. Summary In this article, we review the significance of serum carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and CA 72-4 in GC. The results from different studies regarding the diagnostic and prognostic role of CA 19-9, CEA, and CA 72-4 in GC are encouraging, but inadequate sensitivity and specificity obstruct their use as standardized and unconditionally reliable markers in GC. New prospective clinical trials are mandatory for clarifying their value in GC. Key Message CA 19-9, CEA, and CA 72-4 should not be used for screening and early diagnosis in GC, whereas they are beneficial in the detection of late GC. CA 19-9, CEA, and CA 72-4 could be used as prognostic and monitoring tools in GC, and their combined measurement in shorter periods of time is the best method to increase sensitivity and specificity. Practical Implications Serum CA 19-9, CEA, and CA 72-4 are useful diagnostic and prognostic tumor markers in GC.
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Affiliation(s)
- Andrey Iskrenov Kotzev
- Clinic of Gastroenterology, University Hospital "Alexandrovska," Medical University Sofia, Sofia, Bulgaria
| | - Peter Vassilev Draganov
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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