Abstract 5277: Proteome and transcriptome alterations in black endometrial cancer patients correlate with poor disease outcome

Abstract

Abstract Objective: Black endometrial cancer patients are more than twice as likely to die from their disease as White patients. This study sought to identify alterations in the proteome and transcriptome of primary tumor tissues from White and Black endometrioid endometrial cancer (EEC) patients associated with differential outcome. Methods: An integrated proteomic and transcriptomic analysis (LC-MS/MS and RNA-seq) was performed on White (n=13) and Black (n=17) EEC patient tissues. Significant and concordantly altered protein and transcript candidates were validated against publicly available RNA-seq data (TCGA UCEC) from White (n=216) and Black (n=49) EEC patients. Validated candidates were further correlated with overall (OS, n=356 White and Black patients) and progression-free survival (PFS, n=331 White and Black patients) to identify candidates significantly associated with differential disease outcome. Alterations of outcome-associated candidates were validated in an independent cohort of White (n=115) and Black (n=17) EEC patient transcript expression data. Results: We identified and validated 89 proteins and transcripts significantly altered between White vs Black EEC patients. Pathway analyses revealed candidates elevated in White EEC patients correlated with marked activation of molecular signaling pathways regulating viral infection, but inhibition of those regulating cell death and necrosis. Candidates elevated in Black EEC patients largely correlated with activation of cell viability and nucleic acid metabolism, but inhibition of cell death, glucose metabolism disorder and inflammatory signaling. Correlation with patient outcome measures revealed 11 candidates significantly associated with differential OS and 8 candidates with differential PFS in EEC patients. All outcome-associated candidates elevated in White patients significantly correlated with a low risk of poor OS and poor PFS (Hazard Ratio (HR) < 1, Wald p-value < 0.05). Conversely, the majority of outcome-associated candidates (88%) elevated in Black patients correlated with a high risk of poor OS and poor PFS (HR > 1, Wald p-value < 0.05). Several OS (27%) and PFS (75%) candidates remained significant after adjustment for disease stage and grade as well as myometrial invasion. Alteration trends for several OS (27%) and PFS (25%) candidates were validated in an independent cohort of White and Black EEC patients. Conclusions: Our analyses identified and confirmed molecular alterations between White and Black EEC patients, including outcome-associated candidates largely supportive of better outcome in White patients, but poor outcome in Black patients. These findings define molecular alterations in White and Black EEC patients consistent with the historic disparity of poor outcome for Black patients warranting further investigation of these candidates in Black EEC disease pathology. Citation Format: Nicholas W. Bateman, Elizabeth Dubil, Guisong Wang, Brian L. Hood, Tracy Litzi, Julie Oliver, Kathleen M. Darcy, Chad A. Hamilton, Thomas P. Conrads, George L. Maxwell. Proteome and transcriptome alterations in black endometrial cancer patients correlate with poor disease outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5277. doi:10.1158/1538-7445.AM2017-5277