Abstract 970: Multi-layer and integrative analysis of the whole transcriptome in Asian gastric cancer: AMPKβ modulation in cancer progression

Abstract

Abstract We performed whole-transcriptome profiling of gastric cancer_the most common cancer in developing countries and the second leading cause of cancer deaths in the world. Applying a innovative SOLiD RNA-Seq approach to 24 gastric tumor samples and 6 noncancerous samples, we generated 3.0 billion short reads to quantitatively measure the abundance of mRNAs and small non-coding RNAs. We then developed a multi-layer analysis to identify differentially expressed mRNAs and microRNAs, and novel single-nucleotide mutations candidates associated with gastric cancer. With the insights from the multi-layer analysis, we experimentally demonstrated a critical role for AMPKβ modulation in gastric cancer progression. This work provides a multi-faceted portrait of the Asian gastric cancer transcriptome, which facilitates the elucidation of molecular mechanisms of gastric carcinogenesis and the development of targeted therapies. By integrating data obtained on the expression of both mRNa and miRNa molecules, we were able to identify certain gene signatures uniquely expressed in gastric cancer. This gene signatures along with gastric cancer-related therapeutic target gene signature, showed molecular changes as robust biological markers. Integration of differentially expressed mRNAs and microRNA profiles allowed us to identify potential miRNA drivers of disease progression. We demonstrated the translational relevance of AMPKβ as a potential therapeutic target for treatment and for prediction of early stage gastric cancer. This work lays a critical foundation for the identification of molecular mechanisms of gastric carcinogenesis and the development of related targeted therapies. 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 970. doi:1538-7445.AM2012-970