Abstract LB-127: Enrichment of chromosome 1 and 6p21 genes associated with worse progression-free and overall survival in endometrial cancer patients

Abstract

Abstract Endometrial cancers are generally considered to have favorable outcomes. However, recurrent, and/or non-endometrioid types and some high-grade endometrioid lesions often have very poor survival with limited treatment options. The genes specifically associated with these poor outcomes are not well described. The integrated genomic characterization of endometrial cancers was published in 2013 and the associated RNA-Seq data of these uterine corpus cancers are publicly available at The Cancer Genome Atlas [Nature 497 (7447):67-73]. However, studies on the association of gene expression with the overall survival and recurrence of these endometrial cancers are not yet reported. In this work, we identify those genes associated with survival and recurrence endpoints. RSEM Normalized RNA-Seq (UNC Illumina HiSeq RNASeq V2, level 3) data was downloaded from the TCGA website and survival data extracted from this resource. Cox regression analysis was performed using the survival package in R-environment. The cohort of the patients used in this study cover a large proportion of endometrioid type, while the remaining are serous and mixed histologic types. The proportion of grades 1 to 3 is 84:101:168 and stages I & II (low) to III & IV (high) is 263:87. The ratio of microsatellite unstable to stable cases is about 1:2 approximately both in living and diseased. The tissues were not micro-dissected leaving tumor infiltrates, stroma and other debris. This analysis identified 160 genes significant at p ≤ 0.001 for either overall survival and recurrence free survival or both. In the overall survival analysis, 82 genes were at hazard ratio (HR) ≥ 1 and 48 were at HR ≤ 1. We noted that chromosome 1 was over-represented among gene locations from these gene transcripts. In addition to enrichment of chromosome 1 genes we noted a cluster of genes located on 6p21 with elevated hazard ratios associated with poor clinical outcome. Ontology analysis of the survival associated genes was assessed by EASE software which pointed out the immune response genes have hazard ratios under 1 suggesting that it is a predominant mechanism associated with positive clinical outcome. The finding of immune response genes association with positive clinical outcome (HR ≤ 1) is provocative that prompts further investigation in the assessment and therapy of endometrial cancer. The enrichment of genes on chromosomes 1 and 6 offer further clues to the mechanisms underlying those endometrial cancers with poor clinical outcome. Citation Format: Rusheeswar Challa, GVR Chandramouli, Alyssa Fedorko, Thomas P. Conrads, John I. Risinger. Enrichment of chromosome 1 and 6p21 genes associated with worse progression-free and overall survival in endometrial cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-127. doi:10.1158/1538-7445.AM2015-LB-127