Abstract
Abstract Background: Gastric cancer is the second cause of cancer-related deaths worldwide. After curative surgery, relapse occurs in a large number of patients except for early gastric cancer patients. Even though within the same stage, gastric cancer patients present diverse clinical manifestations and prognosis. The clinical diversity of gastric cancer arises from the molecular biological diversity, which is caused by changes in different genes. This study aimed to identify potential biomarkers which could be used to classify patients according to prognosis and also become new therapeutic targets. Procedures: We obtained whole genome expression microarray data of 65 primary gastric adenocarcinoma patients and the results were validated by quantitative reverse transcription polymerase chain reaction experiment of 68 gastric cancer tissues. We uncovered prognostic subgroups of gastric cancer and identified expressions of a limited number of genes are significantly associated with prognosis. Immunohistochemical assay using 328 gastric cancer tissues was performed to validate protein levels of biomarker gene. Results: A gene encoding thioredoxin (TXN) was found to be markedly elevated in many gastric cancer tissues and strongly related to poor prognosis (p=0.009) in univariate analysis. Conversely, thioredoxin interacting protein (TXNIP), TXN inhibitor, was significantly decreased in patients with poor prognosis. Systems analysis revealed TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors and also with energy and protein synthesis. It was validated that TXN and TXNIP expression were significant prognostic biomarker even in the same stage patients. When patients were classified into the three groups by expression level of TXN and TXNIP, TXN low and TXNIP high expression group showed better prognosis than others; recurrence free survival (p<0.001) and overall survival (p=0.001). Hypoxia induced gene, ERO1-like (ERO1L), also highly correlated with TXN and this suggested that TXN and TXNIP were influenced by hypoxia in gastric cancer. Conclusion: TXN and TXNIP are promising prognostic markers for gastric cancer and agents that target TXN or up modulate TXNIP could be used in target therapy for gastric cancer patients who are selected based on TXN and TXNIP gene signatures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2268. doi:10.1158/1538-7445.AM2011-2268
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