ABSTRACT
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 352 GC 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 (>5 cm), 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. In vitro 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.
Subject(s)
Biomarkers, Tumor/genetics , Lymphatic Metastasis/genetics , Receptors, CXCR6/genetics , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease-Free Survival , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Invasiveness/genetics , Stomach Neoplasms/pathologyABSTRACT
The objective of this study is to examine the impact of marital status on incidence of metastasis at diagnosis, receipt of surgery, and cause-specific survival (CSS) in patients with gastric cancer (GC). Research data is extracted from The Surveillance, Epidemiology, and End Results (SEER) database, and 18,196 patients diagnosed with GC from 2004 to 2010 are involved. Effects of marital status on incidence of metastasis at diagnosis, receipt of surgery, and CSS are determined using multivariable logistic regression and multivariable Cox regression models, as appropriate. Single GC patients have a higher incidence of metastasis at diagnosis than married patients, while the differences between divorced/separated patients or widowed patients and married patients are not significant. Among those without distant metastasis, single patients, divorced/separated patients, and widowed patients are much less likely to accept surgery compared with married patients. Finally, in the whole group of 18,196 GC patients, single patients, divorced/separated patients, and widowed patients have shorter CSS compared with married patients, even in each of the TNM stage. Marriage had a protective effect against undertreatment and cause-specific mortality (CSM) in GC. Spousal support may contribute to higher rate of surgery receipt and better survival in patients with GC.
