Ero1l, A Novel Prognostic Marker Of Gastric Cancer Patient Survival, Mediates Cancer Cell Invasion And Chemoresistance

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Gastric cancer is the second cause of cancer-related deaths worldwide. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. Molecular markers will be important in predicting patients' outcomes and tailoring personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. We evaluated ERO1L significantly overexpressed in gastric cancer and ERO1L was very highly expressed in hypoxic condition. The other study has identified ERO1L as included in the small group of eight genes predicting poor survival of patients with pulmonary adenocarcinoma. We show that ERO1L is a prognostic marker for overall survival among patients with gastric cancer. To investigate the function of ERO1L gene in gastric cancer cell line (AGS and MKN1), we tested the effect of ERO1L expression on gastric cancer cells. To determine the biologic role of ERO1L in regulating cancer cell proliferation, stable transfection of shRNA and expression vector for ERO1L in gastric cancer cells. Our results showed that shERO1L decrease cell proliferation. Next, we tested whether or not the ERO1L gene is involved in progression to metastatic disease in gastric cancer, especially in tumorigenesis, including migration and invasion. In Functional studies, ERO1L silencing decrease gastric cancer cell migaration and invasion, whereas EROL expression significantly increase cell migration and invasiveness. We examined whether ERO1L plays a role in chemoresistance in gastric cancer cells. After silencing or overexpressing ERO1L, we carried out cell viability assays in gastric cancer cells with a panel of chemotherapy agents used to treat gastric cancer patients: a microtubule stabilizer (paclitaxel) and an antimetabilite (5-FU). Surprisingly, Silencing ERO1L expression led gastric cancer cells to become more sensitive to paclitaxel and 5-FU. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, 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. Citation Format: So-Young Seol, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho. ERO1L, a novel prognostic marker of gastric cancer patient survival, mediates cancer cell invasion and chemoresistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2014-4718