Development of molecular diagnostic and therapeutic target testing using by gene expression profile in gastric cancer

Abstract

Gastric cancer is the second leading cause of global cancer mortality, and it has the highest mortality rates in East Asia, including south korea, Japan and China. We previously identified two prognostic subgroups of patients with gastric cancer through gene expression microarray technology. The gene expression microarray data imply that TXN plays an important role in gastric cancer. Hypoxia-induced gene, ERO1L, was significantly correlated with TXN. Tumors with high TXN expression also exhibited elevated ERO1L. It was highly correlated with TXN (P<0.001). To determine the potential clinicopathologic implication of ERO1L expression, we established two stable cell lines using ERO1L-specific small hairpin RNA (shRNA) in ERO1L high expressing gastric cancer AGS cells. We further investigated the functional role of ERO1L in gastric cancer cell lines. We found that cell proliferation suppression induced by the ERO1L-specific shRNA was caused by inhibition of cell cycle through activation of phosphor-cdc2 expression. Furthermore, demonstrate that a decrease in the ERO1L level markedly influences cell migration and invasion, implying that contributes to the metastasis of gastric cancer (P<0.001).In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Unequal distribution of expression patterns reflecting activation of ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection.