A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer

Abstract

Racial disparities between Black/African Americans (AA) and White patients in colorectal cancer (CRC) is an ever-growing area of concern. Black/AA show the highest incidence and have the highest mortality among major U.S. racial groups. There is no definite cause other than possible sociodemographic, socioeconomic, education, nutrition, delivery of healthcare, screening, and cultural factors. A primary limitation in this field is the lack of and small sample size of Black/AA studies. Thus, this study aimed to investigate whether differences in gene expression contribute to this ongoing unanswered racial disparity issue. In this study, we examined transcriptomic data of Black/AA and White patient cohorts using a bioinformatic and systems biology approach. We performed a Kaplan Meier overall survival analysis between both patient cohorts across critical CRC signal transduction networks (STNs), to determine the differences in significant genes across each cohort. Other bioinformatic analyses performed included PROGENy (pathway responsive genes for activity inference), RNA Sequencing differential expression using DESeq2, multivariable-adjusted regression, and other associated Kaplan Meier analyses. These analyses identified novel prognostic genes independent from each cohort, 176 differentially expressed genes (DEG), and specific patient cohort STN survival associations. Despite the overarching limitation, the results revealed several novel differences in gene expression between the CRC Black/AA and White patient cohorts, which allows one to dive deeper into and understand the behaviour on a systems level of what could be driving this racial difference across CRC. Concretely, this information can guide precision medicine approaches tailored specifically for CRC racial disparities.