High expression of RAB7A is associated with poor prognosis of gastric cancer by promoting tumor invasion

Abstract

To explore the expression level of Ras-related protein 7A (RAB7A) in gastric cancer and its prognostic implications. Based on data from public databases and a cohort of 104 patients undergoing radical gastrectomy for gastric cancer in our hospital, we analyzed RAB7A expression level in gastric cancer and adjacent tissues and its association with clinicopathological parameters and prognosis of the patients. Bioinformatic analysis was performed to predict the pathways of RAB7A to affect gastric cancer invasion. In gastric cancer MGC803 cells with lentivirus-mediated interference or overexpression of RAB7A, the changes in extracellular matrix (ECM) degradation and cell migration and invasion were analyzed using immunoblotting, wound healing assay and Transwell experiments. The data from public cancer databases and clinical samples showed a significantly higher expression of RAB7A in gastric cancer tissues than in normal or adjacent tissues (P<0.01) with a close correlation with a poorer patient survival (P<0.01) and a positive correlation with serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P<0.001). Univariate and multivariate Cox regression analyses suggested that a high RAB7A expression was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR: 2.882; 95% CI: 1.459-5.693). ROC curve analysis showed that at the cut-off value of 2.625, RAB7A expression level had a sensitivity of 84.62% and a specificity of 71.15% for predicting postoperative 5-year mortality of the patients. Bioinformatic analysis suggested that RAB7A was involved in ECM degradation and activation of PI3K/AKT signaling in gastric cancer. MGC803 cells with RAB7A overexpression showed activation of the PI3K/AKT signaling pathway (P<0.01) with enhanced expressions of MMP-2 and MMP-9 (P<0.01) and cell migration and invasion capacities (P<0.01). RAB7A is highly expressed in gastric cancer tissues and affects the patients' prognosis possibly by activating the PI3K/AKT signaling pathway and enhancing ECM degradation to promote tumor invasion.