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Ji HS. Research and analysis of circulating tumor cell detection in the diagnosis and treatment of gastric cancer. World J Gastrointest Oncol 2025; 17:102329. [PMID: 40092958 PMCID: PMC11866229 DOI: 10.4251/wjgo.v17.i3.102329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/27/2024] [Accepted: 12/30/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Circulating tumor cells (CTCs) are crucial for improving our knowledge regarding tumor progress, prognosis, and recurrence possibility. AIM To evaluate the role of CTCs in the early diagnosis and treatment of gastric cancer. METHODS From June 2020 to December 2021, a randomized study was conducted in our institution involving 80 patients scheduled for surgery for gastric cancer. The patients were divided into two groups: A control group that was tested for traditional serum markers and a study group that was assessed for serum CTCs. RESULTS In the study cohort, CTC levels did not correlate significantly with patient age, gender, or degree of tumor differentiation (P > 0.05). However, there was a significant correlation with the tumor-node-metastasis stage of the tumor (P < 0.05). In the study group, the CTC diagnostic positivity rate was 62.50% (25 out of 40 patients), while the positivity rate for conventional serum markers in the control group was 47.50% (19 out of 40 patients). The positive detection rate in the study group was significantly higher than that of the control group (P < 0.05). CONCLUSION CTCs have slight invasion and high sensitivity and specificity, presenting great value for early clinical diagnosis of recurrence and metastasis. It will improve the deceleration of disease development and increase the survival rate.
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Affiliation(s)
- Han-Shu Ji
- Second Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
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Rafiyan M, Tootoonchi E, Golpour M, Davoodvandi A, Reiter RJ, Asemi R, Sharifi M, Rasooli Manesh SM, Asemi Z. Melatonin for gastric cancer treatment: where do we stand? NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1265-1282. [PMID: 39287677 DOI: 10.1007/s00210-024-03451-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 09/10/2024] [Indexed: 09/19/2024]
Abstract
Gastric cancer (GC) is the third leading reason of death in men and the fourth in women. Studies have documented an inhibitory function of melatonin on the proliferation, progression and invasion of GC cells. MicroRNAs (miRNAs) are small, non-coding RNAs that play an important function in regulation of biological processes and gene expression of the cells. Some studies reported that melatonin can suppress the progression of GC by regulating the exosomal miRNAs. Thus, melatonin represents a promising potential therapeutic agent for subjects with GC. Herein, we evaluate the existing data of both in vivo and in vitro studies to clarify the molecular processes involved in the therapeutic effects of melatonin in GC. The data emphasize the critical function of melatonin in several signaling ways by which it may inhibit cancer cell proliferation, decrease chemo-resistance, induce apoptosis as well as limit invasion, angiogenesis, and metastasis. This review provides a resource that identifies some of the mechanisms by which melatonin controls GC enlargement. In light of the findings, melatonin should be considered a novel and testable therapeutic mediator for GC treatment.
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Affiliation(s)
- Mahdi Rafiyan
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Elham Tootoonchi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Mahdieh Golpour
- Student Research Committee, Mazandarn University of Medical Sciences, Sari, Mazandaran, Iran
| | - Amirhossein Davoodvandi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health. Long School of Medicine, San Antonio, TX, USA
| | - Reza Asemi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehran Sharifi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Windon A, Al Assaad M, Hadi K, Mendelson N, Hissong E, Deshpande A, Tranquille M, Mclee J, Levine MF, Patel M, Medina-Martínez JS, Chiu K, Manohar J, Sigouros M, Ocean AJ, Sboner A, Jessurun J, Elemento O, Shah M, Mosquera JM. Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses. Pathol Res Pract 2025; 266:155788. [PMID: 39708521 DOI: 10.1016/j.prp.2024.155788] [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: 12/18/2024] [Accepted: 12/18/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications. METHODS Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients. Mutations and rearrangements in clinically relevant cancer genes were investigated and correlated with OncoKB, a knowledge-based precision oncology database, to identify treatment implications. Genome-wide signatures and manually curated molecular profiles were also determined. RESULTS The analyses revealed 90 targetable oncogenic mutations and fusions in 63 % of the patients, including novel NTRK, NRG1, ALK, and MET fusions, and structural variants in cancer genes like RAD51B. Also, molecular signatures associated with mismatch repair and homologous recombination deficiency were elucidated. Notably, we identified CDK12-type genomic instability associated with CDK12 fusions. CONCLUSIONS Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.
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Affiliation(s)
- Annika Windon
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Majd Al Assaad
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
| | | | - Nicole Mendelson
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Erika Hissong
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
| | | | - Marvel Tranquille
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Justin Mclee
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
| | | | | | | | - Kenrry Chiu
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Jyothi Manohar
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Michael Sigouros
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Allyson J Ocean
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Andrea Sboner
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
| | - José Jessurun
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Olivier Elemento
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
| | - Manish Shah
- Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Juan Miguel Mosquera
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
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Qin X, Qiu B, Ge L, Wu S, Ma Y, Li W. Applying machine learning techniques to predict the risk of distant metastasis from gastric cancer: a real world retrospective study. Front Oncol 2024; 14:1455914. [PMID: 39703842 PMCID: PMC11655338 DOI: 10.3389/fonc.2024.1455914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 11/15/2024] [Indexed: 12/21/2024] Open
Abstract
Background Distant metastasis of gastric cancer can seriously affect the treatment strategy of gastric cancer patients, so it is essential to identify patients at high risk of distant metastasis of gastric cancer earlier. Method In this study, we retrospectively collected research data from 18,472 gastric cancer patients from the SEER database. We applied six machine learning algorithms to construct a model that can predict distant metastasis of gastric cancer. We constructed the machine learning model using 10-fold cross-validation. We evaluated the model using the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, and calibration curves. In addition, we used Shapley's addition interpretation (SHAP) to interpret the machine learning model. We used data from 1595 gastric cancer patients in the First Hospital of Jilin University for external validation. We plotted the correlation heat maps of the predictor variables. We selected an optimal model and constructed a web-based online calculator for predicting the risk of distant metastasis of gastric cancer. Result The study included 18,472 patients with gastric cancer from the SEER database, including 4,202 (22.75%) patients with distant metastases. The results of multivariate logistic regression analysis showed that age, race, grade of differentiation, tumor size, T stage, radiotherapy, and chemotherapy were independent risk factors for distant metastasis of gastric cancer. In the ten-fold cross-validation of the training set, the average AUC value of the random forest (RF) model was 0.80. The RF model performed best in the internal test set and external validation set. The RF model had an AUC of 0.80, an AUPRC of 0.555, an accuracy of 0.81, and a precision of 0.78 in the internal test set. The RF model had a metric AUC of 0.76 in the external validation set, an AUPRC of 0.496, an accuracy of 0.82, and a precision of 0.81. Finally, we constructed a network calculator for distant metastasis of gastric cancer using the RF model. Conclusion With the help of pathological and clinical indicators, we constructed a well-performing RF model for predicting the risk of distant metastasis in gastric cancer patients to help clinicians make clinical decisions.
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Affiliation(s)
- Xinxin Qin
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Binxu Qiu
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Litao Ge
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Song Wu
- Nanjing Luhe People’s Hostipal, General Surgery, Nanjing, China
| | - Yuye Ma
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Wei Li
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
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Li Y, Sun W, Yuan S, Liu X, Zhang Z, Gu R, Li P, Gu X. The role of cuproptosis in gastric cancer. Front Immunol 2024; 15:1435651. [PMID: 39539553 PMCID: PMC11558255 DOI: 10.3389/fimmu.2024.1435651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 08/19/2024] [Indexed: 11/16/2024] Open
Abstract
As a biologically essential transition metal, copper is widely involved in various enzymatic reactions and crucial biological processes in the body. It plays an increasingly important role in maintaining normal cellular metabolism and supporting the growth and development of the human body. As a trace element, copper maintains the dynamic balance of its concentration in body fluids through active homeostatic mechanisms. Both excess and deficiency of copper ions can impair cell function, ultimately leading to cell damage and death. Cuproptosis is a novel form of cell death where copper ions cause cell death by directly binding to the lipoylated components of the citric acid cycle (CAC) in mitochondrial respiration and interfering with the levels of iron-sulfur cluster (Fe-S cluster) proteins, ultimately causing protein toxic stress. Its primary characteristics are Cu2+ concentration dependence and high expression in mitochondrial respiratory cells. Recent research has revealed that, compared to other forms of programmed cell death such as apoptosis, necrosis, and autophagy, cuproptosis has unique morphological and biochemical features. Cuproptosis is associated with the occurrence and development of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. This article focuses on a review of the relevance of cuproptosis in gastric cancer (GC).
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Affiliation(s)
- Yixian Li
- Nanjing University of Chinese Medicine, the First Clinical Medical College, Nanjing, Jiangsu, China
| | - Wenhao Sun
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province, Nanjing, Jiangsu, China
| | - Shaolin Yuan
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province, Nanjing, Jiangsu, China
| | - Xinxin Liu
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province, Nanjing, Jiangsu, China
| | - Ziqi Zhang
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Renjun Gu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Pengfei Li
- Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xin Gu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Park SY, Park JH, Yang JW, Jung EJ, Ju YT, Jeong CY, Kim JY, Park T, Kim TH, Park M, Lee YJ, Jeong SH. SMARCD3 Overexpression Promotes Epithelial-Mesenchymal Transition in Gastric Cancer. Cancers (Basel) 2024; 16:2282. [PMID: 38927986 PMCID: PMC11201906 DOI: 10.3390/cancers16122282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/14/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan-Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16, p < 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial-mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p < 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p < 0.05), and in KATO III cells, it increased β-catenin and PI3Kp85 activities (p < 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT.
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Affiliation(s)
- Sun Yi Park
- Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea (C.-Y.J.)
| | - Ji-Ho Park
- Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea (C.-Y.J.)
| | - Jung Wook Yang
- Department of Pathology, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea
| | - Eun-Jung Jung
- Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea; (E.-J.J.); (T.-H.K.)
| | - Young-Tae Ju
- Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea (C.-Y.J.)
| | - Chi-Young Jeong
- Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea (C.-Y.J.)
| | - Ju-Yeon Kim
- Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea (C.-Y.J.)
| | - Taejin Park
- Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea; (E.-J.J.); (T.-H.K.)
| | - Tae-Han Kim
- Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea; (E.-J.J.); (T.-H.K.)
| | - Miyeong Park
- Department of Anesthesiology, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea
| | - Young-Joon Lee
- Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea (C.-Y.J.)
| | - Sang-Ho Jeong
- Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea; (E.-J.J.); (T.-H.K.)
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Singh T, Sharma D, Sharma R, Tuli HS, Haque S, Ramniwas S, Mathkor DM, Yadav V. The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives. Cancers (Basel) 2024; 16:1711. [PMID: 38730663 PMCID: PMC11083332 DOI: 10.3390/cancers16091711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/18/2024] [Accepted: 04/24/2024] [Indexed: 05/13/2024] Open
Abstract
In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.
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Affiliation(s)
- Tejveer Singh
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi 110007, India; (D.S.); (R.S.)
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences-Defence Research and Development Organization, (INMAS-DRDO) New Delhi, Delhi 110054, India
| | - Deepika Sharma
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi 110007, India; (D.S.); (R.S.)
| | - Rishabh Sharma
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi 110007, India; (D.S.); (R.S.)
- Amity Stem Cell Institute, Amity Medical School, Amity University, Gurugram 122412, India
| | - Hardeep Singh Tuli
- Department of Bio-Sciences & Technology, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala 133207, India;
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; (S.H.); (D.M.M.)
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut 11022801, Lebanon
| | - Seema Ramniwas
- University Centre for Research & Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Gharuan, Mohali 140413, India;
| | - Darin Mansor Mathkor
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; (S.H.); (D.M.M.)
| | - Vikas Yadav
- Department of Translational Medicine, Clinical Research Centre, Skåne University Hospital, Lund University, SE-20213 Malmö, Sweden
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Xu ZY, Hao XY, Wu D, Song QY, Wang XX. Prognostic value of 11-factor modified frailty index in postoperative adverse outcomes of elderly gastric cancer patients in China. World J Gastrointest Surg 2023; 15:1093-1103. [PMID: 37405092 PMCID: PMC10315114 DOI: 10.4240/wjgs.v15.i6.1093] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/15/2023] [Accepted: 04/12/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Preoperative evaluation of frailty is limited to a few surgical procedures. However, the evaluation in Chinese elderly gastric cancer (GC) patients remains blank. AIM To validate and estimate the prognostic value of the 11-index modified frailty index (mFI-11) for predicting postoperative anastomotic fistula, intensive care unit (ICU) admission, and long-term survival in elderly patients (over 65 years of age) undergoing radical GC. METHODS This study was a retrospective cohort study which included patients who underwent elective gastrectomy with D2 Lymph node dissection between April 1, 2017 and April 1, 2019. The primary outcome was 1-year all-cause mortality. The secondary outcomes were admission to ICU, anastomotic fistula, and 6-mo mortality. Patients were divided into two groups according to the optimal grouping cutoff of 0.27 points from previous studies: High risk of frailty marked as mFI-11High and low risk of frailty marked as mFI-11Low. Survival curves between the two groups were compared, and univariate and multivariate regression analyses were performed to explore the relationship between preoperative frailty and postoperative complications in elderly patients undergoing radical GC. The discrimination ability of the mFI-11, prognostic nutritional index, and tumor-node-metastasis pathological stage to identify adverse postoperative outcomes was assessed by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS A total of 1003 patients were included, of which 13.86% (139/1003) were defined as having mFI-11High and 86.14% (864/1003) as having mFI-11Low. By comparing the incidence of postoperative complications in the two groups of patients, it was found that mFI-11High patients had higher rates of 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality than the mFI-11Low group (18.0% vs 8.9%, P = 0.001; 31.7% vs 14.7%, P < 0.001; 7.9% vs 2.8%, P < 0.001; and 12.2% vs 3.6%, P < 0.001). Multivariate analysis revealed mFI-11 as an independent predictive indicator for postoperative outcome [1-year postoperative mortality: Adjusted odds ratio (aOR) = 4.432, 95% confidence interval (95%CI): 2.599-6.343, P = 0.003; admission to ICU: aOR = 2.058, 95%CI: 1.188-3.563, P = 0.010; anastomotic fistula: aOR = 2.852, 95%CI: 1.357-5.994, P = 0.006; 6-mo mortality: aOR = 2.438, 95%CI: 1.075-5.484, P = 0.033]. mFI-11 showed better prognostic efficacy in predicting 1-year postoperative mortality [area under the ROC curve (AUROC): 0.731], admission to ICU (AUROC: 0.776), anastomotic fistula (AUROC: 0.877), and 6-mo mortality (AUROC: 0.759). CONCLUSION Frailty as measured by mFI-11 could provide prognostic information for 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality in patients over 65 years old undergoing radical GC.
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Affiliation(s)
- Zi-Yao Xu
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Xin-Yu Hao
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Di Wu
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Qi-Ying Song
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Xin-Xin Wang
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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9
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Gastric Cancer Subtypes in Tumour and Nontumour Tissues by Immunologic and Hallmark Gene Sets. JOURNAL OF ONCOLOGY 2022; 2022:7887711. [PMID: 36065314 PMCID: PMC9440817 DOI: 10.1155/2022/7887711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 07/15/2022] [Accepted: 07/18/2022] [Indexed: 11/17/2022]
Abstract
A previous research study on differentiating gastric cancer (GC) into distinct subtypes or prognostic models was mostly based on GC tissues, which neglected the role of nontumour tissues in GC subtypes. The purpose of the research was to identify GC subtypes on the basis of tumour and adjacent nontumour tissues to assess the prognosis of GC patients. We characterized three GC subtypes on the basis of the immunologic and hallmark gene sets in GC and adjacent nontumour tissues: among them, the GC patients with subtype I had the longest survival time compared to patients with other subtypes. The classification was closely associated with T stage and pathological stage of GC patients. A prognostic model containing two gene sets was constructed by LASSO analysis. Kaplan–Meier analysis showed that patients in the high-risk group survived longer than those in the low-risk group and the two prognostic genes sets in the model were strongly correlated with survival status. Then, GO and KEGG analyses and PPI network show that nontumour and tumour tissues are influencing the prognosis of GC patients in separate manners. In summary, we emphasized the prognostic value of nontumour tissue in GC patients and proposed a novel insight that both changes in tumour and nontumour tissues should be taken into account when selecting a treatment strategy for GC.
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10
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Zhang S, Li X, Tang C, Kuang W. Inflammation-Related Long Non-Coding RNA Signature Predicts the Prognosis of Gastric Carcinoma. Front Genet 2021; 12:736766. [PMID: 34819945 PMCID: PMC8607501 DOI: 10.3389/fgene.2021.736766] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 10/05/2021] [Indexed: 12/25/2022] Open
Abstract
Background: Gastric carcinoma (GC) is a molecularly and phenotypically highly heterogeneous disease, making the prognostic prediction challenging. On the other hand, Inflammation as part of the active cross-talk between the tumor and the host in the tumor or its microenvironment could affect prognosis. Method: We established a prognostic multi lncRNAs signature that could better predict the prognosis of GC patients based on inflammation-related differentially expressed lncRNAs in GC. Results: We identified 10 differently expressed lncRNAs related to inflammation associated with GC prognosis. Kaplan-Meier survival analysis demonstrated that high-risk inflammation-related lncRNAs signature was related to poor prognosis of GC. Moreover, the inflammation-related lncRNAs signature had an AUC of 0.788, proving their utility in predicting GC prognosis. Indeed, our risk signature is more precise in predicting the prognosis of GC patients than traditional clinicopathological manifestations. Immune and tumor-related pathways for individuals in the low and high-risk groups were further revealed by GSEA. Moreover, TCGA based analysis revealed significant differences in HLA, MHC class-I, cytolytic activity, parainflammation, co-stimulation of APC, type II INF response, and type I INF response between the two risk groups. Immune checkpoints revealed CD86, TNFSF18, CD200, and LAIR1 were differently expressed between lowand high-risk groups. Conclusion: A novel inflammation-related lncRNAs (AC015660.1, LINC01094, AL512506.1, AC124067.2, AC016737.1, AL136115.1, AP000695.1, AC104695.3, LINC00449, AC090772.1) signature may provide insight into the new therapies and prognosis prediction for GC patients.
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Affiliation(s)
- ShuQiao Zhang
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - XinYu Li
- Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - ChunZhi Tang
- Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - WeiHong Kuang
- Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
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11
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Ning FL, Zhang NN, Wang J, Jin YF, Quan HG, Pei JP, Zhao Y, Zeng XT, Abe M, Zhang CD. Prognostic value of modified Lauren classification in gastric cancer. World J Gastrointest Oncol 2021; 13:1184-1195. [PMID: 34616522 PMCID: PMC8465445 DOI: 10.4251/wjgo.v13.i9.1184] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/01/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It remains controversial as to which pathological classification is most valuable in predicting the overall survival (OS) of patients with gastric cancer (GC). AIM To assess the prognostic performances of three pathological classifications in GC and develop a novel prognostic nomogram for individually predicting OS. METHODS Patients were identified from the Surveillance, Epidemiology, and End Results program. Univariate and multivariate analyses were performed to identify the independent prognostic factors. Model discrimination and model fitting were evaluated by receiver operating characteristic curves and Akaike information criteria. Decision curve analysis was performed to assess clinical usefulness. The independent prognostic factors identified by multivariate analysis were further applied to develop a novel prognostic nomogram. RESULTS A total of 2718 eligible GC patients were identified. The modified Lauren classification was identified as one of the independent prognostic factors for OS. It showed superior model discriminative ability and model-fitting performance over the other pathological classifications, and similar results were obtained in various patient settings. In addition, it showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting 3- and 5-year OS. A novel prognostic nomogram incorporating the modified Lauren classification showed superior model discriminative ability, model-fitting performance, and net benefits over the American Joint Committee on Cancer 8th edition tumor-node-metastasis classification. CONCLUSION The modified Lauren classification shows superior net benefits over the Lauren classification and tumor differentiation grade in predicting OS. A novel prognostic nomogram incorporating the modified Lauren classification shows good model discriminative ability, model-fitting performance, and net benefits.
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Affiliation(s)
- Fei-Long Ning
- Department of General Surgery, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou 221000, Jiangsu Province, China
| | - Nan-Nan Zhang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi’an 710000, Shannxi Province, China
| | - Jun Wang
- Department of General Surgery, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou 221000, Jiangsu Province, China
| | - Yi-Feng Jin
- Department of General Surgery, Jiading Hospital of Traditional Chinese Medicine, Shanghai 201800, China
| | - Hong-Guang Quan
- Department of General Surgery, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou 221000, Jiangsu Province, China
| | - Jun-Peng Pei
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Yan Zhao
- Department of Stomach Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
| | - Xian-Tao Zeng
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Evidence-Based Medicine and Clinical Epidemiology, The Second Clinical College of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Masanobu Abe
- Division for Health Service Promotion, The University of Tokyo, Tokyo 113-0033, Japan
| | - Chun-Dong Zhang
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
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Daniyal M, Liu Y, Yang Y, Xiao F, Fan J, Yu H, Qiu Y, Liu B, Wang W, Yuhui Q. Anti-gastric cancer activity and mechanism of natural compound "Heilaohulignan C" isolated from Kadsura coccinea. Phytother Res 2021; 35:3977-3987. [PMID: 34155704 DOI: 10.1002/ptr.7114] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/20/2021] [Accepted: 03/25/2021] [Indexed: 12/11/2022]
Abstract
In this research, we analyzed the antitumor activity of one new compound Heilaohulignan C (B-6) on the human gastric carcinoma cells. MTT, cell migration, Calcein AM/Propidium Iodide (PI), and flow cytometry in BGC-823 cell line (gastric tumor). Western blot was utilized to distinguish the protein level. Xenografts nude mice were used for in vivo anticancer analysis. H&E staining and laboratory investigation was accomplished for toxicity study. MTT test demonstrated the cytotoxicity of BGC-823 cells, Calcein AM/Propidium Iodide (PI) examine indicated increment dead cells proportion with a high dose of B-6, Flow cytometry (FACS) measure showed that B-6 influenced gastric cancer cells by initiating apoptosis. Western blot analysis confirmed that (B-6) decrease the level of Bcl-2 and increase the level of p53, Bax, and cleaved Caspase-3, this confirms that the B-6 doing the apoptosis through caspase and cytochrome C apoptotic pathways. Also, B-6 particularly decline the tumor volume and tumor size in the xenograft mice. H&E staining additionally supports that B-6 does not have any toxic impact on the normal tissues. This research supports that B-6 have pharmacological activity against gastric cancer, by p53 and mitochondrial dependent apoptotic pathway, and have no toxicity on normal tissues.
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Affiliation(s)
- Muhammad Daniyal
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yongbei Liu
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yupei Yang
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Feng Xiao
- College of Biology, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan University, Changsha, Hunan, China
| | - Jialong Fan
- College of Biology, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan University, Changsha, Hunan, China
| | - Huanghe Yu
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yixing Qiu
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Bin Liu
- College of Biology, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan University, Changsha, Hunan, China
| | - Wei Wang
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Qin Yuhui
- TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
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13
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Shetty NP, Prabhakaran M, Srivastava AK. Pleiotropic nature of curcumin in targeting multiple apoptotic-mediated factors and related strategies to treat gastric cancer: A review. Phytother Res 2021; 35:5397-5416. [PMID: 34028111 DOI: 10.1002/ptr.7158] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/21/2021] [Accepted: 04/30/2021] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) is one of the major reasons for cancer-associated death and exhibits the second-highest mortality rate worldwide. Several advanced approaches have been designed to treat GC; however, these strategies possess many innate complications. In view of this, the upcoming research relying on natural products could result in designing potential anticancer agents with fewer side effects. Curcumin, isolated from the rhizomes of Curcuma longa L. has several medicinal properties like antiinflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic. Such pleiotropic nature of curcumin impedes the invasion and proliferation of GC by targeting several oncogenic factors like p23, human epidermal factor receptor2 including Helicobacter pylori. The side effect of chemotherapy, that is, chemotherapeutic resistance and radiotherapy could be reduced combination therapy of curcumin. Moreover, the photodynamic therapy of curcumin destroys the cancer cells without affecting normal cells. However, further more potential studies are required to establish the potent efficacy of curcumin in the treatment of GC. The current review details the anticancer activities of curcumin and related strategies which could be employed to treat GC with additional focus on its inhibitory properties against viability, proliferation, and migration of GC cells through cell cycle arrest and stimulation by apoptosis-mediated factors.
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Affiliation(s)
- Nandini P Shetty
- Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570020, India
| | - Manoj Prabhakaran
- Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570020, India
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Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer. Biosci Rep 2021; 41:227392. [PMID: 33345281 PMCID: PMC7796188 DOI: 10.1042/bsr20202564] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 11/24/2020] [Accepted: 12/15/2020] [Indexed: 12/13/2022] Open
Abstract
Background: The present study aimed to use bioinformatics tools to explore pivotal genes associated with the occurrence of gastric cancer (GC) and assess their prognostic significance, and link with clinicopathological parameters. We also investigated the predictive role of COL1A1, THBS2, and SPP1 in immunotherapy. Materials and methods: We identified differential genes (DEGs) that were up- and down-regulated in the three datasets (GSE26942, GSE13911, and GSE118916) and created protein–protein interaction (PPI) networks from the overlapping DEGs. We then investigated the potential functions of the hub genes in cancer prognosis using PPI networks, and explored the influence of such genes in the immune environment. Results: Overall, 268 overlapping DEGs were identified, of which 230 were up-regulated and 38 were down-regulated. CytoHubba selected the top ten hub genes, which included SPP1, TIMP1, SERPINE1, MMP3, COL1A1, BGN, THBS2, CDH2, CXCL8, and THY1. With the exception of SPP1, survival analysis using the Kaplan–Meier database showed that the levels of expression of these genes were associated with overall survival. Genes in the most dominant module explored by MCODE, COL1A1, THBS2, and SPP1, were primarily enriched for two KEGG pathways. Further analysis showed that all three genes could influence clinicopathological parameters and immune microenvironment, and there was a significant correlation between COL1A1, THBS2, SPP1, and PD-L1 expression, thus indicating a potential predictive role for GC response to immunotherapy. Conclusion: ECM–receptor interactions and focal adhesion pathways are of great significance in the progression of GC. COL1A1, THBS2, and SPP1 may help predict immunotherapy response in GC patients.
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15
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Lindblad A, Kaucher S, Jaehn P, Kajüter H, Holleczek B, Lissner L, Becher H, Winkler V. The Incidence of Intestinal Gastric Cancer among Resettlers in Germany-Do Resettlers Remain at an Elevated Risk in Comparison to the General Population? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17249215. [PMID: 33317154 PMCID: PMC7763658 DOI: 10.3390/ijerph17249215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/02/2020] [Accepted: 12/07/2020] [Indexed: 12/24/2022]
Abstract
Objective: Previous studies have shown that the incidence of gastric cancer (GC), and particularly intestinal GC, is higher among resettlers from the former Soviet Union (FSU) than in the general German population. Our aim was to investigate if the higher risk remains over time. Methods: GC cases between 1994 and 2013, in a cohort of 32,972 resettlers, were identified by the respective federal cancer registry. Age-standardized rates (ASRs) and standardized incidence ratios (SIRs) were analyzed in comparison to the general population for GC subtypes according to the Laurén classification. Additionally, the cohort was pooled with data from a second resettler cohort from Saarland to investigate time trends using negative binomial regression. Results: The incidence of intestinal GC was elevated among resettlers in comparison to the general population (SIR (men) 1.64, 95% CI: 1.09–2.37; SIR (women) 1.91, 95% CI: 1.15–2.98). The analysis with the pooled data confirmed an elevated SIR, which was stable over time. Conclusion: Resettlers’ higher risk of developing intestinal GC does not attenuate towards the incidence in the general German population. Dietary and lifestyle patterns might amplify the risk of GC, and we believe that further investigation of risk behaviors is needed to better understand the development of disease pattern among migrants.
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Affiliation(s)
- Anna Lindblad
- Heidelberg Institute of Global Health, University Hospital Heidelberg, 69120 Heidelberg, Germany; (A.L.); (S.K.)
| | - Simone Kaucher
- Heidelberg Institute of Global Health, University Hospital Heidelberg, 69120 Heidelberg, Germany; (A.L.); (S.K.)
| | - Philipp Jaehn
- Institute of Social Medicine and Epidemiology, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany;
| | | | | | - Lauren Lissner
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 41346 Gothenburg, Sweden;
| | - Heiko Becher
- Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
| | - Volker Winkler
- Heidelberg Institute of Global Health, University Hospital Heidelberg, 69120 Heidelberg, Germany; (A.L.); (S.K.)
- Correspondence:
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16
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Shah MA, Enzinger P, Ko AH, Ocean AJ, Philip PA, Thakkar PV, Cleveland K, Lu Y, Kortmansky J, Christos PJ, Zhang C, Kaur N, Elmonshed D, Galletti G, Sarkar S, Bhinder B, Pittman ME, Plotnikova OM, Kotlov N, Frenkel F, Bagaev A, Elemento O, Betel D, Giannakakou P, Lenz HJ. Multicenter Phase II Study of Cabazitaxel in Advanced Gastroesophageal Cancer: Association of HER2 Expression and M2-Like Tumor-Associated Macrophages with Patient Outcome. Clin Cancer Res 2020; 26:4756-4766. [PMID: 32641434 PMCID: PMC8209413 DOI: 10.1158/1078-0432.ccr-19-3920] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 03/31/2020] [Accepted: 07/01/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE We examined cabazitaxel, a novel next-generation taxoid, in patients with metastatic gastric cancer in a multicenter phase II study. PATIENTS AND METHODS Patients who have progressed on one or more prior therapies for locally advanced, unresectable, or metastatic disease were eligible, and prior taxane therapy was allowed. Taxane-naïve and pretreated cohorts were analyzed independently for efficacy. The primary endpoint for both cohorts was progression-free survival (PFS) using RECIST 1.1, using a Simon's two-stage design (10% significance and 80% power) for both cohorts. Comprehensive molecular annotation included whole exome and bulk RNA sequencing. RESULTS Fifty-three patients enrolled in the taxane-naïve cohort (Arm A) and 23 patients in the prior-taxane cohort (Arm B), from January 8, 2013, to April 8, 2015: median age 61.7 years (range, 35.5-91.8 years), 66% male, 66% Caucasian. The most common adverse events included neutropenia (17% Arm A and 39% Arm B), fatigue/muscle weakness (13%), and hematuria (12%). In Arm A, the 3-month PFS rate was 28% [95% confidence interval (CI), 17%-42%] and did not meet the prespecified efficacy target. The 3-month PFS rate in Arm B was 35% (95% CI, 16%-57%) and surpassed its efficacy target. HER2 amplification or overexpression was associated with improved disease control (P = 0.003), PFS (P = 0.04), and overall survival (P = 0.002). An M2 macrophage signature was also associated with improved survival (P = 0.031). CONCLUSIONS Cabazitaxel has modest activity in advanced gastric cancer, including in patients previously treated with taxanes. Her2 amplification/overexpression and M2 high macrophage signature are potential biomarkers for taxane efficacy that warrant further evaluation.
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Affiliation(s)
- Manish A Shah
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
- Englander Institute of Precision Medicine, Meyer Cancer Center, New York, New York
| | - Peter Enzinger
- Dana-Farber Cancer Center, Medical Oncology, Boston, Massachusetts
| | - Andrew H Ko
- University of California San Francisco, Medical Oncology, San Francisco, California
| | - Allyson J Ocean
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Philip Agop Philip
- Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Prashant V Thakkar
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Kyle Cleveland
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Yao Lu
- Division of Biostatistics and Epidemiology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Jeremy Kortmansky
- Yale Cancer Center, Division of Medical Oncology and Hematology, New Haven, Connecticut
| | - Paul J Christos
- Division of Biostatistics and Epidemiology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Chao Zhang
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York
| | - Navjot Kaur
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Dina Elmonshed
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Giuseppe Galletti
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Sandipto Sarkar
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Bhavneet Bhinder
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
- Englander Institute of Precision Medicine, Meyer Cancer Center, New York, New York
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York
| | - Meredith E Pittman
- Department of Anatomic and Clinical Pathology, Weill Cornell, New York, New York
| | | | | | | | | | - Olivier Elemento
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York
| | - Doron Betel
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York
| | - Paraskevi Giannakakou
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Heinz-Josef Lenz
- University of Southern California, Norris Cancer Center, Medical Oncology, Los Angeles, California
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Bahrami A, A Ferns G. Effect of Curcumin and Its Derivates on Gastric Cancer: Molecular Mechanisms. Nutr Cancer 2020; 73:1553-1569. [PMID: 32814463 DOI: 10.1080/01635581.2020.1808232] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Gastric carcinoma is one of the most prevalent malignancies and is associated with a high mortality. Chemotherapy is the principal therapeutic option in the treatment of gastric cancer, but its success rate is restricted by severe side effects and the prevalence of chemo-resistance. Curcumin is a polyphenolic compound derived from turmeric that has potent antioxidant, anti-inflammatory and anti-tumor effects. There is accumulating evidence that curcumin may prevent gastric cancer through regulation of oncogenic pathways. Furthermore some curcumin analogues and novel formulation of curcumin appear to have anti-tumor activity. The aim of this review was to give an overview of the therapeutic potential of curcumin and its derivatives against gastric cancer in preclinical and clinical studies.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Brighton, Sussex, UK
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HDAC3-dependent transcriptional repression of FOXA2 regulates FTO/m6A/MYC signaling to contribute to the development of gastric cancer. Cancer Gene Ther 2020; 28:141-155. [PMID: 32655129 DOI: 10.1038/s41417-020-0193-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 06/17/2020] [Accepted: 06/24/2020] [Indexed: 12/21/2022]
Abstract
As one of the deadliest malignancies, gastric cancer (GC) is often accompanied by a low 5-year survival following initial diagnosis, which accounts for a substantial proportion of cancer-related deaths each year worldwide. Altered epigenetic modifications of cancer oncogenes and tumor suppressor genes emerge as novel mechanisms have been implicated the pathogenesis of GC. In the current study, we aim to elucidate whether histone deacetylase 3 (HDAC3) exerts oncogenic role in GC, and investigate the possible mechanism. Initially, we collected 64 paired cancerous and noncancerous tissues surgically resected from GC patients. Positive expression of HDAC3, FTO, and MYC in the tissues was measured using Immunohistochemistry. Meanwhile, GC cell line BGC-823/AGS was selected and treated with lentivirus vectors for alteration of HDAC3, FTO, or FOXA2 expressions, followed by detection on mRNA and protein levels of HDAC3, FOXA2, FTO, and MYC using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The results demonstrated that the expressions of HDAC3, FTO and MYC were upregulated, while FOXA2 expression was downregulated in GC tissues and cells. After that, the cell viability, migration, and invasion of GC cells were assessed by CCK-8 and Transwell assays, revealing that HDAC3 accelerated GC cell viability, migration and invasion by degrading FOXA2. Subsequently, the binding relationship among HDAC3, FOXA2, FTO, and MYC was assessed by assays of immunoprecipitation, dual-luciferase reporter gene, and chromatin immunoprecipitation assay. Methylation of m6A mRNA in GC cells was detected via gene-specific m6A qPCR and dot-blot assays. The transcription factor FOXA2 was found to bind to the FTO gene promoter and decreased its expression, while FTO stabilized MYC mRNA by reducing m6A methylation of MYC in GC cells. In addition, HDAC3 was observed to maintain the FTO/m6A/MYC signaling and regulated GC progression, which was also supported by in vivo animal study data of GC cell tumorigenesis in nude mice. These key observations uncover the tumor-initiating activities of HDAC3 in GC through its regulation on FOXA2-mediated FTO/m6A/MYC axis, highlighting the potential of therapeutically targeting epigenetic modifications to combat GC.
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Helicobacter pylori Infection Facilitates the Expression of Resistin-like Molecule Beta in Gastric Carcinoma and Precursor Lesions. Curr Med Sci 2020; 40:95-103. [PMID: 32166670 DOI: 10.1007/s11596-020-2151-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 04/08/2019] [Indexed: 10/24/2022]
Abstract
Helicobacter pylori (H. pylori) was reported to be associated with gastric carcinogenesis. Resistin-like molecule beta (RELMβ), a recently described goblet cell-specific protein, was demonstrated to aberrantly express in gastric cancer and correlated with its clinicopathological features. This study aimed to examine the association between H. pylori and RELMβ expression in gastric carcinoma and precursor lesions. H. pylori infection and RELMβ expression were immunohistochemically evaluated in gastric biopsies from 230 patients. The biopsies consisted of normal gastric mucosa (n=20), mucosa with chronic gastritis (n=41), intestinal metaplasia (n=42), dysplasia (n=31), intestinal-type adenocarcinoma (n=56), and diffuse-type adenocarcinoma (n=40). RELMβ expression was measured in gastric biopsies after H. pylori eradication therapy in a subgroup of 32 patients. Cultured gastric cancer cell line SGC-7901 was infected with H. pylori strains, and RELMβ expression was detected by reverse transcription PCR, real-time PCR and Western blotting. Higher RELMβ immunoreactivity was observed in H. pylori-positive intestinal metaplasia (P=0.003), dysplasia (P=0.032), intestinal-type (P=0.037) and diffuse-type adenocarcinomas (P=0.001) than in H. pylori-negative specimens. Expression rates of RELMβ in dysplasia (P=0.005), intestinal-type adenocarcinoma (P<0.001), and diffuse-type adenocarcinoma (P=0.001) were significantly correlated with the grade of H. pylori density. In addition, H. pylori eradication reduced the RELMβ intensity in intestinal metaplasia (P=0.001). Infection of gastric cancer SGC-7901 cells with cag pathogenicity island (PAI)-positive H. pylori TN2, but not with its PAI totally deleted mutant (TN2-ΔPAI) for 4-8 h, resulted in enhanced protein and transcript levels of RELMβ (P<0.05). In summary, our study suggested that H. pylori infection facilitated the expression of RELMβ in gastric garcinoma and precursor lesions.
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Kim B, Nam SK, Seo SH, Park KU, Ahn SH, Park DJ, Kim HH, Kim WH, Lee HS. Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR. Sci Rep 2020; 10:4177. [PMID: 32144300 PMCID: PMC7060190 DOI: 10.1038/s41598-020-60897-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 02/17/2020] [Indexed: 01/18/2023] Open
Abstract
In this study, we measured the human epidermal growth factor receptor 2 (HER2) copy number in both tissue and plasma samples of gastric cancer patients by using droplet digital polymerase chain reaction (ddPCR) method. Eighty gastric cancer patients were enrolled and both formalin-fixed and paraffin-embedded tissue and preoperative plasma samples were collected. HER2 status was determined by HER2 immunohistochemistry (IHC)/silver in situ hybridization (SISH) in tissue samples and ddPCR of the target gene HER2 and the reference gene eukaryotic translation initiation factor 2C, 1 in both tissue and plasma. The concordance rate of tissue HER2 status determined by IHC/SISH and HER2 ddPCR was 90.0% (72/80), and the sensitivity and specificity of tissue ddPCR were 85.0% and 95.0%, respectively. The concordance rate of plasma ddPCR and IHC/SISH was 63.8% (51/80). The sensitivity, specificity, positive predictive value, and negative predictive value of plasma HER2 ddPCR were 37.5%, 90.0%, 79.0%, and 59.0%, respectively. As HER2 measurement by tissue ddPCR showed a high concordance rate with HER2 status by IHC/SISH, it could replace tissue IHC/SISH testing in gastric cancer. These findings may contribute to the development of tissue and plasma HER2 testing that would be useful in daily practice.
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Affiliation(s)
- Boram Kim
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.,Department of Laboratory Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea
| | - Soo Kyung Nam
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea
| | - Soo Hyun Seo
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.,Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea
| | - Kyoung Un Park
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.,Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.,Department of Surgery, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.,Department of Surgery, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea
| | - Woo Ho Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea. .,Department of Pathology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
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21
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Cai H, Hou X, Ding Y, Fu Z, Wang L, Du Y. Prediction of gastric cancer prognosis in the next-generation sequencing era. TRADITIONAL MEDICINE AND MODERN MEDICINE 2019. [DOI: 10.1142/s2575900019300029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide, and is caused by complex interactions of multiple risk factors such as environmental (Helicobacter pylori and Epstein–Barr Virus), hereditary (genetic alterations and epigenetic modifications), as well as dietary and lifestyle factors. GC is usually detected at an advanced stage, with a dismal prognosis. Even for patients with similar clinical or pathologic stage receiving similar treatment, the outcomes are still uneven and unpredictable. To better incorporate genetic and epigenetic profiles into GC prognostic predication, gene expression signatures have been developed to predict GC outcomes. More recently, the advancement of high-throughput sequencing technology, also known as next-generation sequencing (NGS) technology, and analysis has provided the basis for accurate molecular classification of GC tumors. Here, we summarized and updated the literature related to NGS studies of GC, including whole-genome sequencing, whole-exome sequencing, RNA sequencing, and targeted sequencing, and discussed current progresses. NGS has facilitated the identification of genetic/epigenetic targets for screening as well as development of targeted agent therapy, thus enabling individualized patient management and treatment.
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Affiliation(s)
- Hui Cai
- Department of General Surgery, Changhai Hospital, Second Military Medical University Shanghai, 200433, P. R. China
| | - Xiaomei Hou
- PLA Marine Corps Hospital, Chaozhou, Guangdong 521000, P. R. China
| | - Yibo Ding
- Department of Epidemiology, Second Military Medical University, Shanghai 200433, P. R. China
| | - Zhongxing Fu
- Ningguo Bio-Leader Biotechnology Co., Ltd., Anhui, Hefei, P. R. China
| | - Ling Wang
- Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200090, P. R. China
- Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
- Shanghai Key Laboratory of Female Reproductive, Endocrine-related Diseases, Shanghai, P. R. China
| | - Yan Du
- Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200090, P. R. China
- Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
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22
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Lv X, Zhao Y, Zhang L, Zhou S, Zhang B, Zhang Q, Jiang L, Li X, Wu H, Zhao L, Wei M, He M. Development of a novel gene signature in patients without Helicobacter pylori infection gastric cancer. J Cell Biochem 2019; 121:1842-1854. [PMID: 31633246 DOI: 10.1002/jcb.29419] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 10/08/2019] [Indexed: 02/06/2023]
Abstract
Gastric cancer (GC) is one of the most fatal common cancers in worldwide. Helicobacter pylori (H. pylori) infection is closely related to the development of GC, although the mechanism is still unclear. In our study, we aim to develop a robust messenger RNA (mRNA) signature associated with H. pylori (-) GC that can sensitively and efficiently predict the prognostic. The RNA-seq expression profile and corresponding clinical data of 598 gastric cancer samples and 63 normal samples obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Using gene set enrichment analysis H. pylori (+) GC and H. pylori (-) GC patients and normal samples to select certain genes for further analysis. Using univariate and multivariate Cox regression model to establish a gene signature for predicting the overall survival (OS). Finally, we identified G2/M related seven-mRNA signature (TGFB1, EGF, MKI67, ILF3, INCENP, TNPO2, and CHAF1A) closely related to the prognosis of patients with H. pylori (-) GC. The seven-mRNA signature was identified to act as an independent prognostic biomarker by stratified analysis and multivariate Cox regression analysis. It was also validated on two test groups from TCGA and GSE15460 and shown that patients with high-risk scores based on the expression of the seven mRNAs had significantly shorter survival times compared to patients with low-risk scores (P < .0001). In this study, we developed a seven-mRNA signature related to G2/M checkpoint from H. pylori (-) GCs that as an independent biomarker potentially with a good performance in predicting OS and might be valuable for the clinical management for patients with GC.
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Affiliation(s)
- Xuemei Lv
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Yanyun Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Liwen Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Shuqi Zhou
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Bing Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Qiang Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Longyang Jiang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Xueping Li
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Huizhe Wu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Lin Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Miao He
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
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23
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Brar G, Shah MA. The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma. Therap Adv Gastroenterol 2019; 12:1756284819869767. [PMID: 31516556 PMCID: PMC6724489 DOI: 10.1177/1756284819869767] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 07/22/2019] [Indexed: 02/04/2023] Open
Abstract
Gastric cancer is a leading cause of cancer-related death worldwide. Recent evidence suggests that gastric cancer is a complex and heterogenous disease with emerging subtypes shown to affect response to treatment and survival. Immunotherapy is an advancing field and immune checkpoint inhibitors have become standard treatment options in numerous tumor types. In this review, we discuss the current and evolving use of checkpoint blockade, focusing on the anti-PD-1 inhibitor, pembrolizumab, for use in advanced gastric and gastroesophageal cancers.
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Affiliation(s)
- Gagandeep Brar
- Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
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24
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Abstract
Background. Management of gastric cancer (GC) with liver metastases is debated. It is still controversial whether surgical resection provides a survival benefit or not. This systematic review was designed to evaluate the efficacy of hepatectomy for GC liver metastasis. Methods. We searched several electronic databases to identify eligible studies updated on September 2018. Studies assessing the efficacy and safety of hepatectomy versus no hepatectomy were included. Odds ratio (OR) along with 95% confidence interval (95% CI) were utilized for main outcome analysis. Results. In all, 10 studies were included. Patients who underwent hepatectomy had lower 1-year (OR = 0.15, 95% CI = 0.10-0.22, P < .00001), 3-year (OR = 0.16, 95% CI = 0.10-0.27, P < .00001), and 5-year mortality (OR = 0.13, 95% CI = 0.07-0.24, P < .00001) than those without hepatectomy. We also reported favorable survival outcome in patients with metachronous hepatic resection versus synchronous hepatic resection (OR = 2.09, 95% CI = 1.21-3.60, P = .008). However, there was no significant difference between solitary and multiple liver metastases (OR = 0.61, 95% CI = 0.35-1.07, P = .08). Conclusion. The present study demonstrates that hepatic resection in the management of liver metastases of GC can prolong the survival of patients and should be considered a promising treatment for such patients. Furthermore, there are more favorable outcomes in patients with metachronous metastases versus those with synchronous disease. Therefore, metachronous hepatic metastases from GC are not necessarily a contraindication for hepatectomy of the metastatic site.
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Affiliation(s)
- Jun-Kai Cui
- Department of Hepatobiliary Surgery, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, China
| | - Mei Liu
- Department of Intensive Care Unit, Wuhan No. 1 Hospital, Wuhan, China
| | - Xiao-Ke Shang
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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25
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Zheng S, Yang L, Dai Y, Jiang L, Wei Y, Wen H, Xu Y. Screening and Survival Analysis of Hub Genes in Gastric Cancer Based on Bioinformatics. J Comput Biol 2019; 26:1316-1325. [PMID: 31233344 DOI: 10.1089/cmb.2019.0119] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Screening for hub genes associated with gastric cancer and elucidating possible molecular mechanisms of gastric cancer. Five gastric cancer-related gene expression profiles were extracted from the GEO database, and differentially expressed genes (DEGs) were obtained using GEO2R. Gene ontology (GO) enrichment analyses were performed by DAVID, and protein-protein interaction (PPI) network of the DEGs was constructed by STRING and Cytoscape software. Survival value for hub gene comes from the Kaplan-Meier plotter platform. In addition, potential miRNAs of hub genes were predicted by miRWalk. Four hundred seventy-six DEGs were identified in the five expression profiles, these genes are mainly involved in extracellular matrix (ECM)-receptor interaction, chemical carcinogenesis, gastric acid secretion, and PI3K-Akt signaling pathway. Combined with the results of the PPI network and CytoHubba, six hub genes were screened: SERPINH1, NPY, PTGDR, GPER, ADHFE1, and AKR1C1. These genes are highly expressed in gastric cancer tissues, and the overexpression level of these genes is associated with poor survival. A series of miRNAs such as hsa-miRNA-92a-1, hsa-miRNA-647, and hsa-miRNA-507 may play a key role in hub gene regulation. Our studies indicate that SERPINH1, NPY, PTGDR, GPER, ADHFE1, and AKR1C1 may be potential biomarkers and therapeutic targets for gastric cancer in the future.
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Affiliation(s)
- Shunxin Zheng
- Department of Clinical Laboratory, Liuzhou Tanzhong People's Hospital, Liuzhou, P.R. China
| | - Liuhong Yang
- Reproductive Medicine Centre, Liuzhou Maternal and Children Healthcare Hospital, Liuzhou, P.R. China
| | - Yisong Dai
- Department of Clinical Laboratory, Liuzhou Tanzhong People's Hospital, Liuzhou, P.R. China
| | - Lifang Jiang
- Department of Clinical Laboratory, Liuzhou Tanzhong People's Hospital, Liuzhou, P.R. China
| | - Yi Wei
- Department of Clinical Laboratory, Liuzhou Tanzhong People's Hospital, Liuzhou, P.R. China
| | - Hongwei Wen
- Department of Clinical Laboratory, Liuzhou Tanzhong People's Hospital, Liuzhou, P.R. China
| | - Yingfang Xu
- Department of Clinical Laboratory, Liuzhou Tanzhong People's Hospital, Liuzhou, P.R. China
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26
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Cheng C, Wang Q, Zhu M, Liu K, Zhang Z. Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients. Cancer Cell Int 2019; 19:123. [PMID: 31080364 PMCID: PMC6505118 DOI: 10.1186/s12935-019-0846-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 05/02/2019] [Indexed: 12/24/2022] Open
Abstract
Background Increasing evidences supported the association between long non-coding RNA (lncRNA) and disease free survival in gastric cancer (GC) patients. The purpose of the current study was to construct and verify a noninvasive preoperative predictive tool for disease free survival in GC patients. Methods There were 265 and 300 GC patients in model dataset and validation dataset respectively. The associations between the lncRNA biomarkers and disease free survival were evaluated by univariate and multivariate Cox regression. Results Thirteen lncRNA biomarkers (GAS5-AS1, AL109615.3, KDM7A-DT, AP000866.2, KCNJ2-AS1, LINC00656, LINC01777, AC046185.3, TTTY14, LINC01526, LINC02523, LINC00592, and C5orf66) were identified as prognostic biomarkers with disease free survival. These thirteen lncRNA biomarkers were combined to construct a prognostic signature for disease free survival. The C-indexes of the current predictive signature in model cohort were 0.849 (95% CI 0.803–0.895), 0.859 (95% CI 0.813–0.905) and 0.888 (95% CI 0.842–0.934) for 1-year, 3-year and 5-year disease free survival respectively. Based on thirteen-lncRNA prognostic signature, patients in model cohort could be stratified into high risk group and low risk group with significant different disease free survival rate (hazard ratio [HR] = 7.355, 95% confidence interval [CI] 4.378–12.356). Good reproducibility of thirteen-lncRNA prognostic signature was confirmed in an external validation cohort (GSE62254) with HR 3.919 and 95% CI 2.817–5.453. Further analysis demonstrated that the prognostic significance of thirteen-lncRNA prognostic signature was independent of other clinical characteristics. Conclusions In conclusion, a simple noninvasive prognostic signature was established for preoperative prediction of disease free survival in GC patients. This prognostic signature might predict the individual mortality risk of disease free survival without pathological information and facilitate individual treatment decision-making. Electronic supplementary material The online version of this article (10.1186/s12935-019-0846-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Canchang Cheng
- 1Department of Internal Medicine, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong China
| | - Qicai Wang
- 2Department of General Surgery, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong China
| | - Minggu Zhu
- 1Department of Internal Medicine, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong China
| | - Kelong Liu
- 2Department of General Surgery, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong China
| | - Zhiqiao Zhang
- 1Department of Internal Medicine, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong China
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Hassanalilou T, Ghavamzadeh S, Khalili L. Curcumin and Gastric Cancer: a Review on Mechanisms of Action. J Gastrointest Cancer 2019; 50:185-192. [DOI: 10.1007/s12029-018-00186-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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28
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Li B, Lou G, Zhou J. MT1‑MMP promotes the proliferation and invasion of gastric carcinoma cells via regulating vimentin and E‑cadherin. Mol Med Rep 2019; 19:2519-2526. [PMID: 30720114 PMCID: PMC6423635 DOI: 10.3892/mmr.2019.9918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 10/23/2018] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to explore the possible effects of membrane‑type 1 matrix metalloproteinase (MT1‑MMP) on gastric carcinoma cells proliferation and invasion. Immunohistochemistry analysis was conducted to measure MT1‑MMP expression level in 15 patients with gastric carcinoma. Subsequently, recombinant short hairpin RNA (shRNA) vectors targeting MT1‑MMP were constructed to silence the expression of MT1‑MMP in gastric carcinoma cells. Then, the inhibitive efficiency was verified via reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The effects of MT1‑MMP silencing on cell proliferation and invasion were detected through Cell Counting Kit‑8 test and Transwell assays. The expression levels of vimentin and epithelial cadherin (E‑cadherin) were detected by RT‑qPCR. The immunohistochemistry analysis results revealed that MT1‑MMP expression in gastric carcinoma tissues was markedly overexpressed compared with non‑cancerous adjacent tissues. The MT1‑MMP expression level in cancer‑derived cell line AGS cells was also significantly increased compared with that in non‑cancer‑derived GES‑1 cells. In addition, the MT1‑MMP expression level in AGS cells was significantly decreased via shRNA transfection. Cell proliferation and invasion were markedly inhibited following knockdown of MT1‑MMP level in AGS cells. These inhibitory effects were associated with the decreased expression of vimentin and increased expression of E‑cadherin. MT1‑MMP was overexpressed in gastric carcinoma cells, and silencing of MT1‑MMP inhibited the proliferation and invasion of cells via regulating the expression of vimentin and E‑cadherin.
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Affiliation(s)
- Bo Li
- Department of Radiotherapy, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, P.R. China
| | - Guochun Lou
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310000, P.R. China
| | - Juying Zhou
- Department of Radiotherapy, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, P.R. China
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29
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Zhu M, Wang Q, Luo Z, Liu K, Zhang Z. Development and validation of a prognostic signature for preoperative prediction of overall survival in gastric cancer patients. Onco Targets Ther 2018; 11:8711-8722. [PMID: 30584329 PMCID: PMC6287660 DOI: 10.2147/ott.s181741] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Background As a serious challenge for public health, the prognosis of gastric cancer patients is still poor. The current study aimed to develop and validate a prognostic signature to predict the overall survival of gastric cancer patients. Patients and methods The dataset in the present study was obtained from The Cancer Genome Atlas database. The present study finally included 343 gastric cancer patients with information on long non-coding RNA (lncRNA) expression and overall survival. Results A prognostic model named Eleven-lncRNA signature was constructed according to the expression values of eleven prognostic lncRNA predictors identified by univariate and multivariate Cox regression model. According to time-dependent receiver operating characteristic curves, the Harrell's concordance indexes of Eleven-lncRNA signature were 0.764 (95% CI 0.720-0.808), 0.776 (95% CI 0.732-0.820), and 0.807 (95% CI 0.763-0.851) for 1-year overall survival, 3-year overall survival, and 5-year overall survival respectively in the model group. In the validation group, the Harrell's concordance indexes of Eleven-lncRNA signature were 0.748 (95% CI 0.704-0.792), 0.794 (95% CI 0.750-0.838), and 0.798 (95% CI 0.754-0.842) for 1-year overall survival, 3-year overall survival, and 5-year overall survival respectively. The gastric cancer patients (n=343) in the model group could be stratified into low-risk group (n=171) and high-risk group (n=172) according to the median of Eleven-lncRNA signature score. Kaplan-Meier survival curves showed that the mortality rate in the high-risk group was significantly poorer than that in the low-risk group (P<0.001). Conclusion The present study constructed and validated a prognostic model named Eleven-lncRNA signature for preoperative individual mortality risk prediction in gastric cancer patients. This Eleven-lncRNA signature can predict the individual mortality risk of gastric cancer patients and is helpful in improving clinical decision making regarding individualized treatment.
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Affiliation(s)
- Minggu Zhu
- Department of Internal Medicine, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong, China,
| | - Qicai Wang
- Department of General Surgery, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong, China
| | - Zhaowen Luo
- Department of Internal Medicine, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong, China,
| | - Kelong Liu
- Department of General Surgery, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong, China
| | - Zhiqiao Zhang
- Department of Internal Medicine, The Affiliated Chencun Hospital of Shunde Hospital, Southern Medical University, Shunde District, Guangdong, China,
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30
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Li YF, Zhang HT, Xin L. Hyaluronic acid-modified polyamidoamine dendrimer G5-entrapped gold nanoparticles delivering METase gene inhibits gastric tumor growth via targeting CD44+ gastric cancer cells. J Cancer Res Clin Oncol 2018; 144:1463-1473. [PMID: 29858680 DOI: 10.1007/s00432-018-2678-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Accepted: 05/22/2018] [Indexed: 01/29/2023]
Abstract
BACKGROUND Gastric cancer (GC) is the second most common leading cause of cancer-related death. Cancer stem cell (CSC) with the mark of CD44 played an important role in GC. rMETase was wildly exploited as chemotherapeutic option for GC. Polymers synthetic nanoparticle drug delivery systems have been commonly used for cancer therapy. With the decorating of Hyaluronic acid (HA), a receptor of CD44, nanoparticles exhibit with good biocompatibility and aqueous solubility. METHODS The characteristic of nanoparticles (NPs) was analyzed by TEM and DLS. The viability and proliferation of GC cells were examined by MTT assays. The levels of CD44, Cyt C, and c-caspase 3 were examined by Western blot. The level of ROS was measured by DCFH-DA assays. The morphology of tissues was detected using hematoxylin-eosin (H&E) stain. Nude mice xenograft models were used to evaluate the effect of HA-PAMAM-Au-METase on GC. RESULTS The transfection of rMETase carried by HA-G5 PAMAM-Au visibly inhibited the proliferation and tumorsphere formation of GC cells through obviously enhancing METase activity. Elevation of METase activity suppressed the proliferation of CD44(+) GC cells through down-regulating MET in cellular supernatant that resulted in the increase of Cyc C and ROS levels. The number of CD44(+) GC cells in nude mice injected with G5 PAMAM-Au-METase decorated by HA was markly declined resulting in the inhibition of tumor growth. CONCLUSION HA-G5 PAMAM-Au-METase significantly suppressed tumor growth of GC by targeted damaging the mitochondrial function of CD44(+) gastric CSCs.
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Affiliation(s)
- Yi-Fan Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, NO. 1 Minde Rd, Nanchang, 330006, People's Republic of China
| | - Hou-Ting Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, NO. 1 Minde Rd, Nanchang, 330006, People's Republic of China
| | - Lin Xin
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, NO. 1 Minde Rd, Nanchang, 330006, People's Republic of China.
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Li CF, Wang DP, Xue YW. Evaluation of a multi-slice spiral computed tomography perfusion for the prediction of the recurrence of gastric cancer. Future Oncol 2018; 14:1953-1963. [PMID: 30043623 DOI: 10.2217/fon-2016-0541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
AIM The study aimed to elucidate the value of multislice spiral computed tomography (MSCT) perfusion for the early prediction of gastric cancer (GC) recurrence. METHODS MSCT perfusion scans were performed to obtain values pertaining to blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS). Logistic regression analysis was employed to evaluate the risk factors of postoperative recurrence in GC. RESULTS The maximum diameter of GC has a positive relationship with PS. The maximum enhancement of GC was positively correlated with BF, blood volume and PS. PS, BF, vascular thrombus and Tumor, Node, Metastasis staging were found to be significant risk factors in relation to the recurrence of GC (p = 0.006, p = 0.002, p < 0.001). CONCLUSION MSCT perfusion is strongly correlated with postoperative recurrence of GC, and PS and BF values, vascular thrombus and Tumor, Node, Metastasis staging were discovered as being prominent factors influencing the recurrence of GC.
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Affiliation(s)
- Chun-Feng Li
- First Gastrointestinal Surgical Ward, The Harbin Medical University Cancer Hospital, Harbin 150081, PR China
| | - Da-Peng Wang
- Human Resources Department, The Harbin Medical University Cancer Hospital, Harbin 150081, PR China
| | - Ying-Wei Xue
- First Gastrointestinal Surgical Ward, The Harbin Medical University Cancer Hospital, Harbin 150081, PR China
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Pyo JH, Lee H, Min YW, Min BH, Lee JH, Kim KM, Yoo H, Ahn S, Kim JJ. Indication for endoscopic treatment based on the risk of lymph node metastasis in patients with Siewert type II/III early gastric cancer. Gastric Cancer 2018; 21:672-679. [PMID: 29243195 DOI: 10.1007/s10120-017-0789-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 12/07/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Because of the poor prognosis of proximal gastric cancers, there is debate as to whether the conventional indications for endoscopic resection can be used. METHODS Among subjects who underwent surgery for esophagogastric junction or gastric cardia cancer, 256 patients with T1 type II/III of the Siewert classification were included in this study. The association of lymph node metastasis (LNM) with each variable was analyzed using logistic regression models. A receiver operating characteristic curve was used to determine the discriminatory ability of the model. Propensity score-matched non-cardia cancer patients were selected to compare LNM and long-term survival rates. RESULTS Of the 256 patients with T1 Siewert II/III gastric cancer, 21 (8.2%) had LNM. Because there was no LNM in T1a cancers, risk factors were analyzed only in patients with T1b. Tumor size (OR 1.42, 95% CI 1.10-1.82, P = 0.007) and lymphovascular invasion (LVI) (OR 5.13, 95% CI 1.88-14.06, P = 0.002) were determined to be predictors of LNM (sensitivity = 66.7% and specificity = 81.6%). Among patients without LVI, the groups with negligible risk for LNM were mucosa-confined cancer, or SM1 cancer with a tumor size ≤3 cm. No LNM was observed in patients satisfying the absolute or extended criteria for endoscopic resection of early gastric cancers. LNM and long-term survival rates of patients with Siewert II/III did not differ significantly compared with matched non-cardia cancer patients. CONCLUSIONS Tumor size and LVI were associated with LNM in patients with early Siewert type II/III gastric cancer, and the expanded indication for endoscopic resection may be used.
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Affiliation(s)
- Jeung Hui Pyo
- Center for Health Promotion, Samsung Medical Center, Seoul, Republic of Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Heejin Yoo
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Soohyun Ahn
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
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Alves LB, Tsukazan MT, Serafim AE, Mendoza R, Padoin AV, Baú PC, Moreira LF. PROGNOSTIC VALUE OF CARCINOEMBRYONIC ANTIGEN LEVELS IN TRANSOPERATIVE PERITONEAL LAVAGE IN PATIENTS WITH GASTRIC CANCER. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2018; 31:e1358. [PMID: 29947692 PMCID: PMC6049989 DOI: 10.1590/0102-672020180001e1358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 02/16/2018] [Indexed: 11/22/2022]
Abstract
Background: The carcinoembryonic antigen level in peritoneal lavage has been showing to be a reliable prognostic factor in gastric cancer. Aim: To identify any association between carcinoembryonic antigen level in peritoneal lavage, in gastric cancer patients, with mortality, peritoneal recurrence, tumor relapse or other prognostic factors. Methods: In total, 30 patients (22 men, 8 women; median age 66 years) with resectable gastric cancer (mainly stage III and IV) were studied. Carcinoembryonic antigen level in peritoneal lavage was detected at operation by immunocytochemical method and a level over 210 ng/g of protein was considered as positive. Results: There were detected 10 positive cases (33.3%) of plCEA levels. These levels were associated with mortality, RR: 2.1 (p=0.018); peritoneal recurrence, OR: 9.0 (p=0.015); and relapse or gastric cancer progression, OR: 27.0 (p=0.001). Conclusion: Increased levels of plCEA fairly predicts mortality, peritoneal recurrence tumor relapse or cancer progression.
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Affiliation(s)
- Letícia Biscaino Alves
- Post-Graduate Program in Surgery, Hospital de Clínicas of Porto Alegre, Federal University of Rio Grande do Sul.,Center for Obesity and Metabolic Syndrome, São Lucas Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
| | | | | | | | - Alexandre Vontobel Padoin
- Center for Obesity and Metabolic Syndrome, São Lucas Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS).,Post-Graduate Program in Medicine and Health Sciences, PUCRS
| | | | - Luis Fernando Moreira
- Post-Graduate Program in Surgery, Hospital de Clínicas of Porto Alegre, Federal University of Rio Grande do Sul
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Li T, Gao X, Han L, Yu J, Li H. Identification of hub genes with prognostic values in gastric cancer by bioinformatics analysis. World J Surg Oncol 2018; 16:114. [PMID: 29921304 PMCID: PMC6009060 DOI: 10.1186/s12957-018-1409-3] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 06/06/2018] [Indexed: 02/07/2023] Open
Abstract
Background Gastric cancer (GC) is a prevalent malignant cancer of digestive system. To identify key genes in GC, mRNA microarray GSE27342, GSE29272, and GSE33335 were downloaded from GEO database. Methods Differentially expressed genes (DEGs) were obtained using GEO2R. DAVID database was used to analyze function and pathways enrichment of DEGs. Protein-protein interaction (PPI) network was established by STRING and visualized by Cytoscape software. Then, the influence of hub genes on overall survival (OS) was performed by the Kaplan-Meier plotter online tool. Module analysis of the PPI network was performed using MCODE. Additionally, potential stem loop miRNAs of hub genes were predicted by miRecords and screened by TCGA dataset. Transcription factors (TFs) of hub genes were detected by NetworkAnalyst. Results In total, 67 DEGs were identified; upregulated DEGs were mainly enriched in biological process (BP) related to angiogenesis and extracellular matrix organization and the downregulated DEGs were mainly enriched in BP related to ion transport and response to bacterium. KEGG pathways analysis showed that the upregulated DEGs were enriched in ECM-receptor interaction and the downregulated DEGs were enriched in gastric acid secretion. A PPI network of DEGs was constructed, consisting of 43 nodes and 87 edges. Twelve genes were considered as hub genes owing to high degrees in the network. Hsa-miR-29c, hsa-miR-30c, hsa-miR-335, hsa-miR-33b, and hsa-miR-101 might play a crucial role in hub genes regulation. In addition, the transcription factors-hub genes pairs were displayed with 182 edges and 102 nodes. The high expression of 7 out of 12 hub genes was associated with worse OS, including COL4A1, VCAN, THBS2, TIMP1, COL1A2, SERPINH1, and COL6A3. Conclusions The miRNA and TFs regulation network of hub genes in GC may promote understanding of the molecular mechanisms underlying the development of gastric cancer and provide potential targets for GC diagnosis and treatment. Electronic supplementary material The online version of this article (10.1186/s12957-018-1409-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ting Li
- Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.,National Clinical Research Center for Cancer, Tianjin, China
| | - Xujie Gao
- Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.,National Clinical Research Center for Cancer, Tianjin, China
| | - Lei Han
- Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.,National Clinical Research Center for Cancer, Tianjin, China
| | - Jinpu Yu
- Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.,National Clinical Research Center for Cancer, Tianjin, China
| | - Hui Li
- Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. .,Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China. .,National Clinical Research Center for Cancer, Tianjin, China.
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35
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Quan R, Huang J, Chen H, Liao Y, Lv W, Chen N, Liu J, Zhang H, Xu D. Comparison of efficacy in adjuvant chemotherapy regimens in patients with radically resected gastric cancer : a propensity-matched analysis. Oncotarget 2018; 7:76316-76326. [PMID: 27602756 PMCID: PMC5342817 DOI: 10.18632/oncotarget.11783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 08/09/2016] [Indexed: 01/23/2023] Open
Abstract
Background We conducted the retrospective study to compare the efficacy of monotherapies versus two-drug regimens as postoperative chemotherapy for patients with radically resected gastric cancer. Result At a median follow-up of 5.3 years, no significant difference in terms of OS was observed between two groups, neither before nor after matching. After matching, median DFS was statistically significant between group A and B (median, 67.5 vs 101.0 months, respectively; hazard ratio [HR], 0.65; 95% CI, 0.45 to 0.95; P=0.027), which meant doublets prolonged DFS. In subgroup analysis, the patients of stage III receiving doublet achieved better OS than those receiving monotherapy. People who received doublet and were less than 65 years old, or male patients, or in T4 stage, or in N2 stage, or receiving subtotal gastrectomy had better DFS than those with monotherapy. Method A data set including 501 patients (monotherapy, n=107; doublet, n=394) was matched between the two groups (n=107 patients per group) using the propensity-matched study. The primary and secondary endpoint was overall survival(OS) and disease-free survival(DFS), respectively. Survival data was compared using the Kaplan-Meier method and Cox proportion hazards models for univariate and multivariate analyses. Conclusion The dual regimens seemed not to add overall survival benefits to patients receiving curative gastrectomy, compared with single-agent fluoropyrimidine as postoperative chemotherapy. However, dual regimens showed better disease-free survival.
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Affiliation(s)
- RenCui Quan
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - JiaXing Huang
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - HongTao Chen
- Department of Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - YiFeng Liao
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - WeiZe Lv
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - Nan Chen
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - JianJun Liu
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, China
| | - HongYu Zhang
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China
| | - DaZhi Xu
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, China
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36
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Zhou X, Men X, Zhao R, Han J, Fan Z, Wang Y, Lv Y, Zuo J, Zhao L, Sang M, Liu XD, Shan B. miR-200c inhibits TGF-β-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer. Cancer Gene Ther 2018; 25:68-76. [DOI: 10.1038/s41417-017-0005-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 10/12/2017] [Accepted: 10/20/2017] [Indexed: 02/08/2023]
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Yu J, Li L, Huang C. Downregulation of Inhibition of Apoptosis-Stimulating Protein of p53 (iASPP) Suppresses Cisplatin-Resistant Gastric Carcinoma In Vitro. Med Sci Monit 2017; 23:5542-5549. [PMID: 29161238 PMCID: PMC5706386 DOI: 10.12659/msm.905403] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) with cisplatin resistance is one of the leading causes of limitations to therapy. Inhibition of apoptosis-stimulating protein of p53 (iASPP) plays a key role in GC. However, the role of iASPP in GC with cisplatin resistance remains unclear. The aim of this study was to investigate iASPP expression in GC, and the functions of iASPP in cisplatin-resistant cell lines. MATERIAL AND METHODS In this study, the expression of iASPP was investigated in normal GC patients and patients with cisplatin resistance, along with GC cell lines and cell lines with cisplatin resistance. Furthermore, knockdown of iASPP was conducted in cell lines; and cell proliferation, apoptosis rate, cell cycle distribution, and cell migration and invasion were determined through CCK8, flow cytometry, Scratch test and Transwell assay, respectively. RESULTS The expression of iASPP in GC patients with cisplatin resistance was significant higher than in the health control group. Higher expression of iASPP was detected in cisplatin-resistant cancer cell lines. Cell proliferation of SGC-7901 and MGC-803 was inhibited by transfection with siRNA, along with evaluated apoptosis rate and G1 phase retardant. Furthermore, cells viability, including migration and invasion, was suppressed post-transfection with siRNA. CONCLUSIONS iASPP induced cisplatin resistance in GC patients. Thus, knockdown of iASPP might be a novel therapeutic strategy for the treatment of GC cisplatin-resistant patients.
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Affiliation(s)
- Jianyong Yu
- Department of General Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Qingdao, Shandong, China (mainland)
| | - Li Li
- Department of Traditional Chinese Medicine (TCM) Orthopedics, The Wendeng Osteopath Hospital, Yantai, Shandong, China (mainland)
| | - Chengsuo Huang
- Department of General Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Qingdao, Shandong, China (mainland)
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Wang S, Han H, Hu Y, Yang W, Lv Y, Wang L, Zhang L, Ji J. MicroRNA-130a-3p suppresses cell migration and invasion by inhibition of TBL1XR1-mediated EMT in human gastric carcinoma. Mol Carcinog 2017; 57:383-392. [PMID: 29091326 DOI: 10.1002/mc.22762] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Revised: 09/24/2017] [Accepted: 10/23/2017] [Indexed: 12/12/2022]
Abstract
MiR-130a-3p was found to play tumor suppressor role in most human cancers, except for gastric cancer. However, in this study, we demonstrated that miR-130a-3p was significantly down-regulated in gastric carcinoma (GC) tissues compared with adjacent non-neoplastic tissues, and decreased miR-130a-3p expression was associated with shorter overall survival (OS) and was an independent prognostic factor for OS in GC patients. Over-expression of miR-130a-3p remarkably inhibited not only GC cell migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, but also tumorigenesis and lung metastasis in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Conversely, inhibition of miR-130a-3p resulted in opposite phenotype changes in GC cells. Furthermore, TBL1XR1 was identified as a direct target of miR-130a-3p, and reintroduction of TBL1XR1 into miR-130a-3p-transfected MGC-803 cells reversed the inhibitory effects of miR-130a-3p on GC cell migration, invasion and EMT. Taken together, our data suggested that miR-130a-3p suppressed aggressive phenotype of GC cells partially by direct targeting and decreasing TBL1XR1 and subsequent EMT process.
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Affiliation(s)
- Shanshan Wang
- Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, P.R. China
| | - Haibo Han
- Department of Biobank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, P.R. China
| | - Ying Hu
- Department of Biobank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, P.R. China
| | - Wei Yang
- Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, P.R. China
| | - Yunwei Lv
- Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, P.R. China
| | - Limin Wang
- Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, P.R. China
| | - Lianhai Zhang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, P.R. China
| | - Jiafu Ji
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, P.R. China
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Chen LT, Oh DY, Ryu MH, Yeh KH, Yeo W, Carlesi R, Cheng R, Kim J, Orlando M, Kang YK. Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review. Cancer Res Treat 2017; 49:851-868. [PMID: 28052652 PMCID: PMC5654167 DOI: 10.4143/crt.2016.176] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 12/20/2016] [Indexed: 02/08/2023] Open
Abstract
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.
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Affiliation(s)
- Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes and National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Do-Youn Oh
- Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Winnie Yeo
- Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China
| | | | | | | | | | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Li L, Feng R, Xu Q, Zhang F, Liu T, Cao J, Fei S. Expression of the β3 subunit of Na +/K +-ATPase is increased in gastric cancer and regulates gastric cancer cell progression and prognosis via the PI3/AKT pathway. Oncotarget 2017; 8:84285-84299. [PMID: 29137423 PMCID: PMC5663595 DOI: 10.18632/oncotarget.20894] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 08/26/2017] [Indexed: 12/13/2022] Open
Abstract
ATP1B3 encodes the β3 subunit of Na+/K+-ATPase and is located in the q22-23 region of chromosome 3. Na+/K+-ATPase participates in normal cellular activities but also plays a crucial role in carcinogenesis. In the present study, we found that expression of the β3 subunit of Na+/K+-ATPase was increased in human gastric cancer tissues compared with that in normal matched tissues and that this increased expression predicted a poor outcome. ATP1B3 expression was elevated at both the mRNA and protein levels in gastric cancer cell lines relative to those in a normal gastric epithelial cell line. Interestingly, ATP1B3 knockdown significantly inhibited cell proliferation, colony-formation ability, migration, and invasion and increased apoptosis in human gastric carcinoma cell lines. Additionally, knockdown induced cell cycle arrest at the G2/M phase. Furthermore, we demonstrated that ATP1B3 silencing decreased the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and phosphorylated AKT (p-AKT), indicating that ATP1B3 regulates gastric cancer cell progression via the PI3K/AKT signalling pathway. Hence, the β3 subunit of Na+/K+-ATPase plays an essential role in the tumourigenesis of gastric cancer and may be a potential prognostic and therapeutic target for the treatment of gastric cancer.
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Affiliation(s)
- Li Li
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Ru Feng
- Department of Gastroenterology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Qian Xu
- Department of Gastroenterology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Feiyue Zhang
- Department of Gastroenterology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Tong Liu
- Department of Gastroenterology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Jiang Cao
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
| | - Sujuan Fei
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
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Petrelli F, Ghidini M, Barni S, Steccanella F, Sgroi G, Passalacqua R, Tomasello G. Prognostic Role of Primary Tumor Location in Non-Metastatic Gastric Cancer: A Systematic Review and Meta-Analysis of 50 Studies. Ann Surg Oncol 2017; 24:2655-2668. [DOI: 10.1245/s10434-017-5832-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Tian X, Zhu X, Yan T, Yu C, Shen C, Hong J, Chen H, Fang JY. Differentially Expressed lncRNAs in Gastric Cancer Patients: A Potential Biomarker for Gastric Cancer Prognosis. J Cancer 2017; 8:2575-2586. [PMID: 28900495 PMCID: PMC5595087 DOI: 10.7150/jca.19980] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 05/10/2017] [Indexed: 12/16/2022] Open
Abstract
Current studies indicate that long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers and implicated with prognosis in gastric cancer (GC). We intended to generate a multi-lncRNA signature to improve prognostic prediction of GC. By analyzing ten paired GC and adjacent normal mucosa tissues, 339 differentially expressed lncRNAs were identified as the candidate prognostic biomarkers in GC. Then we used LASSO Cox regression method to build a 12-lncRNA signature and validated it in another independent GEO dataset. An innovative 12-lncRNA signature was established, and it was significantly associated with the disease free survival (DFS) in the training dataset. By applying the 12-lncRNA signature, the training cohort patients could be categorized into high-risk or low-risk subgroup with significantly different DFS (HR = 4.52, 95%CI= 2.49-8.20, P < 0.0001). Similar results were obtained in another independent GEO dataset (HR=1.58, 95%CI=1.05 - 2.38, P=0.0270). Further analysis showed that the prognostic value of this 12-lncRNA signature was independent of AJCC stage and postoperative chemotherapy. Receiver operating characteristic (ROC) analysis showed that the area under receiver operating characteristic curve (AUC) of combined model reached 0.869. Additionally, a well-performed nomogram was constructed for clinicians. Moreover, single-sample gene-set enrichment analysis (ssGSEA) showed that a group of pathways related to drug resistance and cancer metastasis significantly enriched in the high risk patients. A useful innovative 12-lncRNA signature was established for prognostic evaluation of GC. It might complement clinicopathological features and facilitate personalized management of GC.
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Affiliation(s)
- Xianglong Tian
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Xiaoqiang Zhu
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Tingting Yan
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Chenyang Yu
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Chaoqin Shen
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Jie Hong
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Haoyan Chen
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
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Wang S, Han H, Hu Y, Yang W, Lv Y, Wang L, Zhang L, Ji J. SLC3A2, antigen of mAb 3G9, promotes migration and invasion by upregulating of mucins in gastric cancer. Oncotarget 2017; 8:88586-88598. [PMID: 29179459 PMCID: PMC5687629 DOI: 10.18632/oncotarget.19529] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 04/17/2017] [Indexed: 11/25/2022] Open
Abstract
Solute carrier family 3 member 2 (SLC3A2) has been reported to be highly expressed in a variety of carcinomas. However, the function of SLC3A2 in gastric carcinoma (GC) has not been well explored. Monoclonal antibody (mAb) 3G9, generated from immunogen of various human GC cell lines, has been shown to bind to GC tissues specifically. In this study, we identified the target antigen of mAb 3G9 as SLC3A2, and detected the expression profile of SLC3A2 in a panel of gastric cancer cell lines and GC tumor tissues. We found that the increased expression of SLC3A2 was associated with serosal invasion in GC patients. Knockout of SLC3A2 suppressed the migration and invasion of BGC-823 cells in vitro and in vivo, whereas overexpression of SLC3A2 in NCI-N87 cells promoted the migration and invasion in vitro and in vivo. Mechanistic investigations suggested that MUC1, MUC16 and MUC5B were the downstream genes of SLC3A2 in GC cells. Taken together, our data suggested that SLC3A2 promoted the aggressive phenotype of GC by upregulating several mucin genes expression and may serve as a potential biomarker for diagnosis and target therapy.
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Affiliation(s)
- Shanshan Wang
- Department of Clinical Laboratory, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, PR China
| | - Haibo Han
- Department of Biobank, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, PR China
| | - Ying Hu
- Department of Biobank, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, PR China
| | - Wei Yang
- Department of Clinical Laboratory, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, PR China
| | - Yunwei Lv
- Department of Clinical Laboratory, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, PR China
| | - Limin Wang
- Department of Clinical Laboratory, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, PR China
| | - Lianhai Zhang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, PR China
| | - Jiafu Ji
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, PR China
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Immunotherapeutic Strategies for Gastric Carcinoma: A Review of Preclinical and Clinical Recent Development. BIOMED RESEARCH INTERNATIONAL 2017; 2017:5791262. [PMID: 28781967 PMCID: PMC5525095 DOI: 10.1155/2017/5791262] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 06/08/2017] [Indexed: 01/09/2023]
Abstract
Gastric carcinoma (GC) is the 2nd most common cause of cancer-related death. Despite advances in conventional treatment and surgical interventions, a high percentage of GC patients still have poor survival. Recently, immunotherapy has become a promising approach to treat GC. Here, we present preclinical and clinical studies encouraging the use of vaccination, adoptive T-cell therapy (ACT), and immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The ongoing immunotherapy clinical trials have shown promising results in safety and tolerability even in late-stage GC patients. Moreover, we highlight that the combination of ACT with chemotherapy could be the best choice to treat GC.
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Popa E, Schnoll‐Sussman F, Jesudian A, Nandakumar G, Shah MA. Uncommon Cancers of the Stomach. TEXTBOOK OF UNCOMMON CANCER 2017:395-415. [DOI: 10.1002/9781119196235.ch27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Shah MA. Future Directions in Improving Outcomes for Patients with Gastric and Esophageal Cancer. Hematol Oncol Clin North Am 2017; 31:545-552. [PMID: 28501093 DOI: 10.1016/j.hoc.2017.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
"This issue of Hematology/Oncology Clinics of North America provides an update to the current understanding of the physiology of gastric and esophageal cancers and the state-of-the-art management of disease. Over the past 10 years, we have witnessed dramatic changes in both our understanding of the disease and its management. We have 2 new biological agents approved to treat advanced disease, with several more prospects under development. In this article, the author looks to the future, attempting to answer the question of which advancements will play the biggest role in improving patient outcomes in this still-devastating disease.
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Affiliation(s)
- Manish A Shah
- Weill Cornell Medicine/New York-Presbyterian Hospital, Division of Hematology and Medical Oncology, 1305 York Avenue, New York, NY 10021, USA.
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Ryu B, Kim SY, Vo TS, Kim WS, Kim DG, Kim SK. Characterization of the in vitro effects of gallic acid-grafted-chitooligosaccharides in the suppression of AGS human gastric cancer cell proliferation. RSC Adv 2017. [DOI: 10.1039/c7ra02487h] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
G-COS was compared with COS for its influence on the proliferation of AGS human gastric cancer cells, showing an increase in the accumulation of cells in the sub-G1 phase and early apoptosis.
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Affiliation(s)
- BoMi Ryu
- Department of Marine Life Science
- Jeju National University
- Republic of Korea
| | - So-Yeon Kim
- Marine Bioprocess Research Center
- Pukyong National University
- Busan 608-739
- Republic of Korea
| | - Thanh-Sang Vo
- NTT Institute of Hi-Technology
- Nguyen Tat Thanh University
- Ho Chi Minh City
- Vietnam
| | - Won-Suk Kim
- Major in Pharaceutical Engineering Division of Bio-Industry
- Silla University
- Busan
- Korea
| | - Dong Gyu Kim
- Specialized Graduate School Science and Technology Convergence
- Department of Marine Bio Convergence Science
- Pukyong National University
- Busan 608-737
- Republic of Korea
| | - Se-Kwon Kim
- Marine Bioprocess Research Center
- Pukyong National University
- Busan 608-739
- Republic of Korea
- Specialized Graduate School Science and Technology Convergence
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Adeshuko FA, Squires MH, Poultsides G, Pawlik TM, Weber SM, Schmidt C, Votanopoulos K, Fields RC, Maithel SK, Cardona K. A Multi-Institutional Study Comparing the Use of the American Joint Committee on Cancer 7th Edition Esophageal versus Gastric Staging System for Gastroesophageal Junction Cancer in a Western Population. Am Surg 2017. [DOI: 10.1177/000313481708300130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by Tor N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population.
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Affiliation(s)
- Folashade A. Adeshuko
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Malcolm H. Squires
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | | | | | - Sharon M. Weber
- Department of Surgical Oncology, University of Wisconsin, Madison, Wisconsin
| | - Carl Schmidt
- Division of Surgical Oncology, Ohio State University, Columbus, Ohio
| | | | - Ryan C. Fields
- Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Shishir K. Maithel
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
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hsa-miR-376c-3p Regulates Gastric Tumor Growth Both In Vitro and In Vivo. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9604257. [PMID: 27965982 PMCID: PMC5124681 DOI: 10.1155/2016/9604257] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 08/10/2016] [Indexed: 11/18/2022]
Abstract
Background. In recent studies, aberrant expression of various microRNAs (miRNAs) is reported to be associated with gastric cancer metastasis. Method. Overexpression construct and inhibitor of hsa-miR-376c-3p were expressed in human gastric adenocarcinoma cell line SGC-7901. The expression level of tumor related genes was detected by qPCR, western blot, and immunostaining. Cell apoptosis was determined by flow cytometry. Xenograft of SGC-7901 cells was used to elucidate the function of hsa-miR-376c-3p in gastric tumor growth in vivo. Result. Expression of hsa-miR-376c-3p was detected in SGC-7901 cells. Downregulation of hsa-miR-376c-3p increased the expression level of BCL-2 and decreased the expression of smad4 and BAD. On the contrary, overexpression of hsa-miR-376c-3p increased the expression of BAD and smad4, while it led to the decreasing expression level of BCL-2. Overexpression of hsa-miR-376c-3p also promoted cell apoptosis in vitro and inhibited gastric tumor growth in vivo. Furthermore, the expression of BCL-2 was higher and expression of smad4 and BAD was lower in tumor tissue than the tissue adjacent to tumor from gastric cancer patients. Conclusion. This study demonstrated that hsa-miR-376c-3p plays an important role in the inhibition of gastric tumor growth and tumor related gene expression both in vitro and in vivo.
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Long D, Yu PC, Huang W, Luo YL, Zhang S. Systematic review of partial hepatic resection to treat hepatic metastases in patients with gastric cancer. Medicine (Baltimore) 2016; 95:e5235. [PMID: 27858875 PMCID: PMC5591123 DOI: 10.1097/md.0000000000005235] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To examine overall survival and mortality following hepatic resection in patients with hepatic metastases from gastric cancer. METHODS EMBASE, PubMed, Web of Science, and Cochrane databases were systematically searched for publications involving more than 10 patients who underwent hepatic resection to treat hepatic metastases from gastric cancer and who did not have peritoneal disease or involvement of other distant organs. RESULTS A total of 39 studies were included, involving a median of 21 hepatic resections (range, 10-64). Resection was associated with median 30-day morbidity of 24% (range, 0%-47%) and 30-day mortality of 0% (range, 0%-30%). Median overall survival was 68% at 1 year, 31% at 3 years, and 27% at 5 years. Asian studies reported higher rates than Western studies for overall survival at 1 year (73% vs 59%), 3 years (34% vs 25%), and 5 years (27% vs 17%). Compared with palliative treatment, resection was associated with significantly lower mortality at 1 year (risk ratio [RR] 0.47, P < 0.001) and 2 years (RR 0.70, P < 0.001). CONCLUSION Patients with hepatic metastases from gastric cancer may benefit from hepatic resection in case of good physical condition, absence of peritoneal dialysis, and optimum liver function with single metastases. More trials are needed to confirm this finding.
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Affiliation(s)
- Di Long
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
- Department of General Surgery, The Second People's Hospital of Qinzhou, Qinzhou, China
| | - Peng-Cheng Yu
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Wei Huang
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Yu-Long Luo
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Sen Zhang
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
- Correspondence: Sen Zhang, Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Rd #22, Nanning 530021, China (e-mail: )
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