Identification Of New Prognostic Biomarker Of Gastric Cancer By Systems Analysis

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Gastric cancer is one of the most common and cancer-related deaths worldwide and accounts for an estimated 800,000 deaths annually. Prognosis depends on the stage of disease. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. To differentiate the malignant potential appropriately, many efforts have been made to select prognostic markers. Molecular markers will be important in predicting patients’ outcomes and 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 which could be used to classify patients according to prognosis and also become new therapeutic targets. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. qRT-PCR and tissue microarray validated TXN overexpression and ERO1L have poor prognosis in gastric cancer. Finally, systems analysis revealed TXN family genes are highly correlated with many oncogene and tumor suppressor functional genes and shown relationship on energy and protein synthesis. Survival analysis based on Hierarchical-clustering of TXN family correlated mRNA expression genes revealed that TXN and TXNIP are significantly influenced the patient survival. We evaluated ERO1L and find out also significantly overexpressed in gastric tumor and suggest TXN family members are actively involved in gastric cancer. In vitro hypoxic experiment ERO1L was very highly expressed in hypoxic condition and this also supports TXN high expressed cancer cells are in hypoxic condition. 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 TXN family and ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4536. doi:1538-7445.AM2012-4536