Abstract 411: Pathway analysis of gene-lists associated with platinum-based chemotherapy resistance in ovarian cancer: the big picture.

Abstract

Abstract Objective. Ovarian cancer is the leading cause of death from gynecological cancers in the Western world [1]. The overall 5-year survival is only 30% [2], which is for a significant part due to platinum-based chemotherapy resistance. In this study, we performed a pathway analysis on nine published gene-sets associated with platinum resistance in ovarian cancer, including a study by us. With this exploratory study, we aim to identify overlapping pathways associated with platinum-based chemotherapy resistance mechanisms in ovarian cancer. Methods A Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA) was performed to determine which functional processes were differentially represented in the combined gene-lists of nine studies (457 genes) compared to all Unigene identifiers or the Ingenuity knowledge base. Results. The GO and IPA analysis resulted in the generation of 23 gene networks, and showed that 13 GO processes (>=2 times enriched), 71 canonical pathways (p<0.05,), eight toxicity pathways (p<.05) and 74 biological functions (p<0.005) are significantly associated with the 9-study gene set. Conclusion and recommendations. Several pathways identified have previously been shown to be associated with therapy resistance: these include ‘oxidative stress response mediated by Nrf2’, ‘TP53 signaling’ and ‘TGFbeta signaling’. The role of TGFbeta signalling as well as related miRNAs identified in the network analysis in epithelial-to-mesenchymal transition (EMT) and stemness as well as the possible relation with platin-based chemotherapy resistance is further discussed in detail. We propose that future international cooperation should aim at a uniform pooled-analysis of the wealth of ovarian cancer array data already available. This will enhance the power of each separate ovarian cancer study and can lead to promising results. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 411.