Disease-free Survival In Gastric Cancer Research Articles

Multitask machine learning-based tumor-associated collagen signatures predict peritoneal recurrence and disease-free survival in gastric cancer.

Accurate prediction of peritoneal recurrence for gastric cancer (GC) is crucial in clinic. The collagen alterations in tumor microenvironment affect the migration and treatment response of cancer cells. Herein, we proposed multitask machine learning-based tumor-associated collagen signatures (TACS), which are composed of quantitative collagen features derived from multiphoton imaging, to simultaneously predict peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). Among 713 consecutive patients, with 275 in training cohort, 222 patients in internal validation cohort, and 216 patients in external validation cohort, we developed and validated a multitask machine learning model for simultaneously predicting peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). The accuracy of the model for prediction of peritoneal recurrence and prognosis as well as its association with adjuvant chemotherapy were evaluated. The TACSPR and TACSDFS were independently associated with peritoneal recurrence and disease-free survival in three cohorts, respectively (all P < 0.001). The TACSPR demonstrated a favorable performance for peritoneal recurrence in all three cohorts. In addition, the TACSDFS also showed a satisfactory accuracy for disease-free survival among included patients. For stage II and III diseases, adjuvant chemotherapy improved the survival of patients with low TACSPR and low TACSDFS, or high TACSPR and low TACSDFS, or low TACSPR and high TACSDFS, but had no impact on patients with high TACSPR and high TACSDFS. The multitask machine learning model allows accurate prediction of peritoneal recurrence and survival for GC and could distinguish patients who might benefit from adjuvant chemotherapy.

Circulating tumor cells are a good predictor of tumor recurrence in clinical patients with gastric cancer

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101–0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169–8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071–0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28–80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.

Mir-605-3p prevents liver premetastatic niche formation by inhibiting angiogenesis via decreasing exosomal nos3 release in gastric cancer.

Cancer-induced pre-metastatic niches (PMNs) play a decisive role in promoting metastasis by facilitating angiogenesis in distant sites. Evidence accumulates suggesting that microRNAs (miRNAs) exert significant influence on angiogenesis during PMN formation, yet their specific roles and regulatory mechanisms in gastric cancer (GC) remain underexplored. miR-605-3p was identified through miRNA-seq and validated by qRT-PCR. Its correlation with the clinicopathological characteristics and prognosis was analyzed in GC. Functional assays were performed to examine angiogenesis both in vitro and in vivo. The related molecular mechanisms were elucidated using RNA-seq, immunofluorescence, transmission electron microscopy, nanoparticle tracking analysis, enzyme-linked immunosorbent assay, luciferase reporter assays and bioinformatics analysis. miR-605-3p was screened as a candidate miRNA that may regulate angiogenesis in GC. Low expression of miR-605-3p is associated with shorter overall survival and disease-free survival in GC. miR-605-3p-mediated GC-secreted exosomes regulate angiogenesis by regulating exosomal nitric oxide synthase 3 (NOS3) derived from GC cells. Mechanistically, miR-605-3p reduced the secretion of exosomes by inhibiting vesicle-associated membrane protein 3 (VAMP3) expression and affects the transport of multivesicular bodies to the GC cell membrane. At the same time, miR-605-3p reduces NOS3 levels in exosomes by inhibiting the expression of intracellular NOS3. Upon uptake of GC cell-derived exosomal NOS3, human umbilical vein endothelial cells exhibited increased nitric oxide levels, which induced angiogenesis, established liver PMN and ultimately promoted the occurrence of liver metastasis. Furthermore, a high level of plasma exosomal NOS3 was clinically associated with metastasis in GC patients. miR-605-3p may play a pivotal role in regulating VAMP3-mediated secretion of exosomal NOS3, thereby affecting the formation of GC PMN and thus inhibiting GC metastasis.

MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions

ABSTRACT Objectives: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. Methods: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. Results: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. Discussion: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

Development of a nomogram based on body composition analysis of quantitative computed tomography combined with clinical prognostic factors to predict disease-free survival after surgery and adjuvant chemotherapy in patients with gastric cancer.

Patients with gastric cancer (GC) have a high recurrence rate after surgery. To predict disease-free survival (DFS), we investigated the value of body composition changes (BCCs) measured by quantitative computed tomography (QCT) in assessing the prognosis of patients with GC undergoing resection combined with adjuvant chemotherapy and to construct a nomogram model in combination with clinical prognostic factors (CPFs). A retrospective study of 60 patients with GC between February 2015 and June 2019 was conducted. Pre- and posttreatment CT images of patients was used to measure bone mineral density (BMD), subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), paravertebral muscle area (PMA), and the rate of BCC was calculated. CPFs such as maximum tumor diameter (MTD), human epidermal growth factor receptor-2 (HER2), and Ki-67 were derived from postoperative pathological findings. Independent prognostic factors affecting DFS in GC were screened via univariate and multivariate Cox regression analysis. The Kaplan-Meier method and log-rank test were used to plot survival curves and compare the curves between groups, respectively. Receiver operating characteristic (ROC) curves, calibration curves, and decision curves to evaluate the efficacy of the nomogram. The results of multivariate Cox regression analysis showed that ΔBMD [hazard ratio (HR): 4.577; 95% confidence interval (CI): 1.483-14.132; P=0.008], ΔPMA (HR: 5.784; 95% CI: 1.251-26.740; P=0.025), HER2 (HR: 4.819; 95% CI: 2.201-10.549; P<0.001), and maximal tumor diameter (HR: 3.973; 95% CI: 1.893-8.337; P<0.001) were independent factors influencing DFS. ΔBMD, ΔSFA, ΔVFA, ΔTFA, and ΔPMA were -3.86%, -23.44%, -19.57%, -22.45%, and -5.94%, respectively. The prognostic model of BCCs combined with CPFs had the highest predictive performance. Decision curve analysis (DCA) indicated good clinical benefit for the prognostic nomogram. The concordance index of the prognostic nomogram was 0.814, and the area under the curve (AUC) of predicting 2- and 3-year DFS were 0.879 and 0.928, respectively. The calibration curve showed that the nomogram-predicted DFS aligned well with the actual DFS. The prognostic nomogram combining BCCs and CPFs was able to reliably predict the DFS of patients with GC.

Association of perioperative allogeneic blood transfusions and long-term outcomes following radical surgery for gastric and colorectal cancers: systematic review and meta-analysis of propensity-adjusted observational studies.

Previous meta-analyses reporting significant associations between perioperative allogeneic blood transfusions and poor prognosis in gastric cancer or colorectal cancer had a high risk of confounding bias. This meta-analysis explored this issue using observational studies that applied propensity score analysis. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for manuscripts published between 2013 and 2022. Studies applying propensity score analysis were included to investigate the association between perioperative allogeneic blood transfusions and prognosis in gastric cancer or colorectal cancer after radical surgery. Pooled HRs for overall survival and disease-free survival were calculated using a fixed-effect model or random-effect model according to heterogeneity. Twelve retrospective cohort studies with 17 607 patients reported were included. Ten studies applied propensity score matching and two applied inverse probability of treatment weighting using propensity score. A total of 5962 patients were analysed after propensity score adjustment. After propensity score adjustment, perioperative allogeneic blood transfusions did not correlate with disease-free survival in gastric cancer (HR 1.16; 95 per cent c.i. 0.96-1.39; heterogeneity was assessed by the chi-squared test and inconsistency index (I2) = 57 per cent) or colorectal cancer (HR 1.12; 95 per cent c.i. 0.84-1.49; I2 = 54 per cent). However, after propensity score adjustment, perioperative allogeneic blood transfusions were significantly associated with worse overall survival in gastric cancer (HR 1.20; 95 per cent c.i. 1.08-1.32; I2 = 25 per cent) and colorectal cancer (HR 1.40; 95 per cent c.i. 1.06-1.85; I2 = 52 per cent). Subgroup analyses showed that perioperative allogeneic blood transfusions did not correlate with overall survival in colorectal cancer when major postoperative complications were balanced after propensity score. Perioperative allogeneic blood transfusion is not correlated with recurrence of gastric cancer and colorectal cancer. Perioperative allogeneic blood transfusions are significantly associated with worse overall survival in gastric cancer and colorectal cancer, which may be attributable to unbalanced major postoperative complications after propensity score adjustment.

A meta-analysis of the association between adjuvant chemoradiotherapy and disease-free survival in gastric cancer according to the histology.

There are biological distinctions between gastric cancers from Eastern and Western nations, and therapeutic strategies may differ regionally. Perioperative chemotherapy, adjuvant chemotherapy, and adjuvant chemoradiotherapy (CRT) have all been demonstrated to be effective in the treatment of gastric cancer. The goal of this study was to do a meta-analysis of published studies that were eligible to see if adjuvant chemoradiotherapy was helpful for gastric cancer based on the cancer's histology. From inception to May 4, 2022, manual searches were conducted to identify all eligible literature using the PubMed database for the published phase III clinical trial and a randomize-controlled trial testing the role of adjuvant chemoradiotherapy in operable gastric cancer. Two trials with a total of 1004 patients were selected as a result. Adjuvant CRT was found to have no effect on disease-free survival (DFS) in gastric cancer patients treated with D2 surgery (HR: 0.70 (0.62-1.02), p: 0.07). However, patients with intestinal-type gastric cancers exhibited significantly longer DFS (HR: 0.58 (0.37-0.92), p = 0.02). After D2 dissection, adjuvant CRT improved DFS in patients with intestinal-type gastric cancers but not in those with diffuse-type gastric cancers.

Intratumoral and Peritumoral Radiomics of Contrast-Enhanced CT for Prediction of Disease-Free Survival and Chemotherapy Response in Stage II/III Gastric Cancer.

BackgroundWe evaluated the ability of radiomics based on intratumoral and peritumoral regions on preoperative gastric cancer (GC) contrast-enhanced CT imaging to predict disease-free survival (DFS) and chemotherapy response in stage II/III GC.MethodsThis study enrolled of 739 consecutive stage II/III GC patients. Within the intratumoral and peritumoral regions of CT images, 584 total radiomic features were computed at the portal venous-phase. A radiomics signature (RS) was generated by using support vector machine (SVM) based methods. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier analysis were used to determine the association of the RS and clinicopathological variables with DFS. A radiomics nomogram combining the radiomics signature and clinicopathological findings was constructed for individualized DFS estimation.ResultsThe radiomics signature consisted of 26 features and was significantly associated with DFS in both the training and validation sets (both P<0.0001). Multivariate analysis showed that the RS was an independent predictor of DFS. The signature had a higher predictive accuracy than TNM stage and single radiomics features and clinicopathological factors. Further analysis showed that stage II/III patients with high scores were more likely to benefit from adjuvant chemotherapy.ConclusionThe newly developed radiomics signature was a powerful predictor of DFS in GC, and it may predict which patients with stage II and III GC benefit from chemotherapy.

Potential Role of Glucose Transporter-1 Expression in Gastric Cancer: A Meta-Analysis and Systematic Review.

Background:Glucose transporter-1 (GLUT-1) has been differentially expressed in various malignancies including gastric cancer (GC). Several previous meta-analyses of GLUT-1 have some significant limitations, such as researching the association between GLUT-1 and various cancer types with no specificity, not studying clinicopathological parameters with GLUT-1, existing conspicuous heterogeneity and so forth. Therefore, we performed a meta-analysis to evaluate the association between GLUT-1 expression and survival of gastric cancer patients, as well as clinicopathological characteristics.Methods:We systematically searched PubMed, Embase, Web of Science and China National Knowledge Infrastructure for relevant studies in accordance with the applicable criteria up to Aug 2017. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were used as the effective measures.Results:A total of 13 studies involving 1972 patients were included in this meta-analysis. The results demonstrated that there was a significant association between GLUT-1 expression and overall survival (OS) (HR=1.45, 95% CI=1.13–1.87) or disease-free survival (DFS) (HR=2.18, 95% CI=1.46–3.25). Moreover, GLUT-1 expression was significantly correlated with worse tumor nodes metastases (TNM) stage (OR=0.34, 95% CI=0.28–0.43), presence of lymph node metastasis (OR=2.88, 95% CI=1.34–6.19), intestinal type of Lauren classification (OR=3.84, 95% CI=2.57–5.74) and invasion of serosa (OR=0.25, 95% CI=0.18–0.35).Conclusion:Our meta-analysis showed that GLUT-1 was significantly correlated with poor OS and DFS in gastric cancer. Additionally, GLUT-1 was also a potential prognostic indicator of aggressive clinicopathological parameters in gastric cancer.

Construction of a Nomogram Based on a Hypoxia-Related lncRNA Signature to Improve the Prediction of Gastric Cancer Prognosis.

BackgroundGastric cancer is one of the most common malignant tumors and has a poor prognosis. Hypoxia is related to the poor prognosis of cancer patients. We searched for hypoxia-related long non-coding RNAs (lncRNAs) to predict both overall survival (OS) and disease-free survival (DFS) of gastric cancer patients.MethodsWe obtained hypoxia-related lncRNA expression profiles and clinical follow-up data of patients with gastric cancer from The Cancer Genome Atlas and the Molecular Signatures Database. The patients were randomly divided into a training group, test group and combined group. The hypoxia-related prognostic signature was constructed by Lasso regression and Cox regression models, the prognoses in different groups were compared by Kaplan–Meier (K-M) analysis, and the accuracy of the prognostic model was assessed by receiver operating characteristic (ROC) analysis.ResultsA hypoxia-related prognostic signature comprising 10 lncRNAs was constructed to predict both OS and DFS in gastric cancer. In the training, test and combined groups, patients were divided into high- and low-risk groups according to the formula. Kaplan–Meier analysis showed that patients in the high-risk group have poor prognoses, and the difference was significant in the subgroup analyses. Receiver operating characteristic analysis revealed that the predictive power of the model prediction is more accurate than that of standard benchmarks. The signature differed across Helicobacter pylori (Hp) status and T stages. Multivariate Cox analysis showed that the signature is an independent risk factor for both OS and DFS. A clinically predictive nomogram combining the lncRNA signature and clinical features was constructed; the nomogram accurately predicted both OS and DFS and had high clinical application value. Weighted correlation network analysis combined with enrichment analysis showed that the primary pathways were the PI3K-Akt, JAK-STAT, and IL-17 signaling pathways. The target genes NOX4, COL8A1, and CHST1 were associated with poor prognosis in the Gene Expression Profiling Interactive Analysis, Gene Expression Omnibus, and K-M Plotter databases.ConclusionsOur 10-lncRNA prognostic signature and nomogram are accurate, reliable tools for predicting both OS and DFS in gastric cancer.

Prognostic Value of C-Reactive Protein to Albumin Ratio in Gastric Cancer: A Meta-Analysis

Objective C-reactive protein to albumin ratio (CRP/Alb) is investigated as a prognostic marker in gastric cancer in previous studies, with presence of inconsistent data. Therefore, this study aimed to explore the prognostic role of CRP/Alb in gastric cancer through meta-analysis. Methods This meta-analysis systemically retrieved PubMed, Embase, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), and Wanfang up to July 4, 2020. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were conducted to evaluate the association between CRP/Alb and survival outcomes. Results A total of nine studies with 3346 patients were included in the present meta-analysis. The pooled HR and 95%CI were: HR = 1.89, 95%CI = 1.64–2.19, p < 0.001 for overall survival (OS) and HR = 2.15, 95%CI = 1.72–2.70, p < 0.001 for disease-free survival (DFS). Subgroup analysis demonstrate that an elevated CRP/Alb remain a significant prognostic factor for poor OS and DFS irrespective of sample size, nationality of patients, or cutoff value resource (p < 0.05 in all subgroups). Conclusions The present meta-analysis suggests that high CRP/Alb is predictive of poor OS and DFS in gastric cancer. CRP/Alb is therefore a potential prognostic factor in the management of patients with gastric cancer.

Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer.

Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.

Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients

BackgroundIncreasing 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.MethodsThere 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.ResultsThirteen 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.ConclusionsIn 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.

ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis.

Genomic alterations of tumor suppressorsoften encompass collateral protein-coding genes that create therapeutic vulnerability to further inhibition of their paralogs. Here, we report that malic enzyme 2 (ME2) is frequently hemizygously codeleted with SMAD4 in gastric cancer. Its isoenzyme ME1 was upregulated to replenish the intracellular reducing equivalent NADPH and to maintain redox homeostasis. Knockdown of ME1 significantly depleted NADPH, induced high levels of reactive oxygen species (ROS), and ultimately cell apoptosis under oxidative stress conditions, such as glucose starvation and anoikis, in ME2-underexpressed cells. Moreover, ME1 promoted tumor growth, lung metastasis, and peritoneal dissemination of gastric cancer in vivo Intratumoral injection of ME1 siRNA significantly suppressed tumor growth in cell lines and patient-derived xenograft-based models. Mechanistically, ME1 was transcriptionally upregulated by ROS in an ETV4-dependent manner. Overexpression of ME1 was associated with shorter overall and disease-free survival in gastric cancer. Altogether, our results shed light on crucial roles of ME1-mediated production of NADPH in gastric cancer growth and metastasis.Significance: These findings reveal the role of malic enzyme in growth and metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/8/1972/F1.large.jpg Cancer Res; 78(8); 1972-85. ©2018 AACR.

CXCR6 predicts poor prognosis in gastric cancer and promotes tumor metastasis through epithelial-mesenchymal transition.

Chemokines and their receptors have been confirmed to be involved in several types of cancer. However, little is known concerning the role of CXCL16 and its receptor CXCR6 in gastric cancer (GC) progression and metastasis. In the present study, expression of CXCL16 and CXCR6 in GC tumor and peritumoral tissues was detected by immunohistochemistry(IHC) in a cohort of 352GC patients who underwent gastrectomy, and the correlation between CXCL16/CXCR6 expression and clinicopathological characteristics was further analyzed. To evaluate the function of CXCR6, we overexpressed and knocked down CXCR6 in GC cell lines. Results showed that expression of CXCR6, but not CXCL16, was significantly upregulated in GC tumor tissues, and was significantly correlated with lymph node and distant metastases, and advanced clinical stage in the GC patients. Survival analysis showed that large tumor size (>5cm), elevated preoperative serum carcinoembryonic antigen (CEA) level, advanced TNM stage and high CXCR6 expression indicated worse overall survival (OS) and disease-free survival (DFS) in GC, and CXCR6 was an independent predictor for both OS and DFS in GC. Invitro experiments showed that CXCR6 overexpression induced cell migration and invasion ability, and promoted epithelial-mesenchymal transition of GC cells by upregulation of mesenchymal markers and inhibition of epithelial markers. In contrast, knockdown of CXCR6 in GC cells resulted in inhibition of cell proliferation, migration and invasion ability, and reversal of epithelial-mesenchymal transition (EMT) phenomenon. Our results demonstrated that CXCR6 is an independent prognostic factor for poor survival in GC patients, and may promote GC metastasis through EMT.

Cyclooxygenase-2 Expression Is Associated with Poor Overall Survival of Patients with Gastric Cancer: A Meta-Analysis

Cyclooxygenase-2 (COX-2) is believed to be involved in gastric carcinogenesis. However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for gastric cancer patients. To obtain a more accurate relationship between COX-2 overexpression and prognosis in gastric cancer by meta-analysis. Relevant articles published up to May 2013 were searched by use of several keywords in electronic databases. Separate hazard ratio (HR) estimates and 95% confidence intervals (95% CI) for COX-2 overexpression and overall survival (OS) and disease-free survival (DFS) with gastric cancer were extracted. Combined HR with 95% CI was calculated by use of Stata11.0 software to estimate the size of the effect. Publication bias testing and sensitivity analysis were also performed. A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. Combined results suggested that COX-2 overexpression was associated with an unfavorable OS (HR 1.58, 95% CI 1.36-1.84) but not DFS (HR 1.15, 95% CI 0.93-1.43) among patients with gastric cancer. Publication bias was absent. Sensitivity analysis suggested that the results of this meta-analysis were robust. The results of this meta-analysis suggest that high COX-2 expression may be an independent risk factor for poor OS of patients with gastric cancer. More large prospective studies are now needed to further clarify the prognostic value of COX-2 expression for DFS in gastric cancer.

Prediction of disease-free survival in gastric cancer using gene expression data

Prediction of disease-free survival in gastric cancer using gene expression data