Abstract 6535: Identification of coding and non-coding genes associated with survival outcomes in uterine cancer
Authors: Ramos Enrique I. , Hidalgo Axel M. , Lin Ken Y. , Gadad Shrikanth S. 
Published: April 2023

Endometrial (or uterine) cancer is the most commonly diagnosed cancer in the female reproductive system and it disproportionately affects Black women, who are twice as likely to die from the disease than White women. In this study, we focused on the molecular characterization of copy-number high (CN-high) molecular subclassification of uterine cancer tumors, which includes most serous and serous-like endometroid tumors. These poorly characterized subcategories account for less than 10% of all uterine cancers but are responsible for over 80% of the mortality in uterine cancers and occur more commonly in Black women.We leveraged publicly available Pan-Cancer Atlas data to perform differential gene expression analyses between control and cancer samples in the Black and White CN-high groups with the aim of identifying relevant genes that could play a role in the aggressiveness of this cancer. We then performed survival analysis using the genes of interest using Kaplan-Meier estimators to ascertain the gene-specific survival outcomes.In the significantly upregulated subset of genes, we found that the high expression of the candidate gene was associated with higher survival in both White patients (p=0.046), and Black patients (p=0.021). Additionally, the expression levels of one of the noncoding genes were associated with differential survival between the groups, with low expression being associated with higher survival in White patients (p=0.0045), and high expression associated with higher survival in Black patients (p=0.018). This differential association of survival was also observed in one of the most downregulated genes in both groups, with low expression predicting higher survival in white patients (p=0.004), and Black patient survival is associated with high expression (p=0.0082). We also identified novel non-coding genes that predicted different survival outcomes in both groups, with high expression predicting better survival in Black patients and low expression predicting better survival in White patients (p=0.048 and p=0.039, respectively). These results showcase the identification of both coding and noncoding potential genomic targets that are associated with clinical outcomes in the aggressive CN-high molecular subtype of uterine cancer. These targets merit further characterization and experimental validation to elucidate their molecular roles in the progression of endometrial cancer.

Acknowledgments S.S.G. is a CPRIT scholar in cancer research and is supported by a First-time Faculty Recruitment Award from the Cancer Prevention and Research Institute of Texas (CPRIT; RR170020). S.S.G. is also supported by a) the Lizanell and Colbert Coldwell Foundation, b) The Edward N. and Margaret G. Marsh Foundation, and c) the American Cancer Society.

Citation Format: Enrique I. Ramos, Axel M. Hidalgo, Ken Y. Lin, Shrikanth S. Gadad. Identification of coding and non-coding genes associated with survival outcomes in uterine cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6535.