Investigating racial disparities in carcinomas through TCGA transcriptomic and proteomic database

Abstract

Simple Summary: Racial disparities in cancer incidence and outcome rates are prevalent in the US, with a variety of contributing factors such as socioeconomic status, differences in lifestyle and environmental exposures, and gene polymorphisms. The goal of this research was to broadly analyze public data to identify critical differences in molecular signatures and pathways between races. Additionally, to ensure the clinical translatability of our work, we analyzed the impact of these differences on patient survival. Our findings will help inform the use of novel biomarkers in clinical settings and the future development of precision therapies. Abstract:Epidemiological studies highlight a disparity in cancer incidence and outcome rates between racial groups in the United States. In our study, we investigated molecular differences among racial groups in 10 carcinoma types. We used publicly available data from The Cancer Genome Atlas to identify patterns of differential gene expression in tumors obtained from 4,112 White, Black/African American, and Asian patients. We identified race-dependent expression of numerous genes whose mRNA transcript levels were significantly correlated with patient survival. A small subset of these genes was differentially expressed in multiple carcinomas, including genes involved in cell cycle progression such as CCNB1, CCNE1, CCNE2, and FOXM1. In contrast, genes such as transcriptional factor ETS1 and apoptotic gene BAK1 were differ-entially expressed and clinically significant only in specific cancer types. Our analyses also revealed race-dependent regulation of relevant pathways. Importantly, homology directed repair and ERBB4-mediated nuclear signaling were both upregulated in Black patients compared to Whites in four carcinoma types. This large-scale pan-cancer study refines our understanding of the cancer health disparity and can help inform the use of novel biomarkers in clinical settings as well as the future development of precision therapies.