Stromal-epithelial metabolic coupling in gastric cancer: stromal MCT4 and mitochondrial TOMM20 as poor prognostic factors.

To explore metabolic symbiosis in gastric cancer and its relationship with cancer prognosis. Immunohistochemistry was used to detect MCT4 and TOMM20 expression in 113 gastric cancer patient specimens. The correlations of MCT4 and TOMM20 expression with gastric cancer clinicopathological features and survival were studied. Stromal MCT4 expression was closely associated with the pathological (p) TNM stage and TOMM20 expression. We also assessed the predictive value of epithelial MCT4 expression. However, no correlation with patient clinical outcome was evident. TOMM20 expression was closely associated with tumor size and stromal MCT4 expression. Further, stromal MCT4 and mitochondrial TOMM20 were positively correlated, and Kaplan-Meier analysis showed that high stromal MCT4 expression and high mitochondrial TOMM20 expression were associated with reduced overall survival and disease-free survival. Both univariate and multivariate analyses revealed that stromal MCT4 expression and mitochondrial TOMM20 expression were independent prognostic factors in gastric cancer patients. Our findings directly support the existence of metabolic symbiosis in gastric cancer. Stromal MCT4 and mitochondrial TOMM20 could be promising biomarkers for predicting the prognosis of patients with gastric cancer. These proteins might also serve as novel therapeutic targets in gastric cancer treatment.