Abstract 5106: A HHIP derived gene expression signature for the prediction of patient survival after adjuvant chemotherapy of pancreatic cancer

Abstract

Abstract Prognosis for patients with pancreatic carcinoma (PDAC) remains poor. Despite of increasing knowledge about the molecular basis of PDAC neither a specific marker for early diagnosis nor target proteins for a new therapeutic approach have been identified so far. However, reliable prediction of survival might help to improve the therapeutic outcome for patients with PDAC. In recent years it has become evident, that the Hedgehog (Hh) signal transduction pathway is a key regulator of pancreatic cancer development. Hedgehog interacting protein (HHIP) is a key modulator of Hh action and is overexpressed in the tumor stroma of PDACs. Reasoning that HHIP could serve as an indicator of Hh signaling activation we identified HHIP associated genes (HAG) using guilt by association (GBA) analysis in a set of PDAC gene expression profiles from microdissected tissue. Using the Affymetrix GeneChip U133 2.0 array and TNASAS we analyzed the gene expression profile of 59 PDAC samples and identified prognostic marker from HAG for survival of PDAC patients with adjuvant therapy. GBA analysis of gene expression profiles from microdissected PDAC tissue yielded 276 HAGs. TNASAS analysis using these genes revealed a prognostic gene expression signature of 50 genes, which was able to identify patients receiving adjuvant therapy with gemcitabine surviving more than 24 month with a total error of 0.087. TNASAS analysis of samples from patients treated without adjuvant therapy failed to identify a gene set with prognostic significance. Gene expression analysis is able to identify genes with prognostic significance in patients with adjuvant chemotherapy. These genes seem to be correlated with the efficacy of adjuvant gemcitabine therapy. Further analysis of those genes can reveal more insights in the signal transduction mechanisms associated with those genes. 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 5106. doi:1538-7445.AM2012-5106