Abstract
BACKGROUND: Black patients with colon cancer (CC) exhibit more aggressive tumor biology and higher treatment resistance than white patients, even after adjusting for clinical and demographic factors. We investigated stage-specific transcriptional differences in tumor profiles of Black and white patients with CC. PATIENTS AND METHODS: Patients with CC from The Cancer Genome Atlas Colon Adenocarcinoma database were categorized by disease stage and propensity-score matched between Black and white patients. Differential gene expression and pathway enrichment analyses were performed for each stage. Logistic regression and quadratic discriminant analysis (QDA) models were developed using consistently differentially expressed genes. RESULTS: Of 247 patients, 128 had localized (22% Black), 81 had regional (74% Black), and 38 had distant disease (29% Black). Differential expression analysis revealed differences in 312 genes for localized, 105 for regional, and 199 for distant stages between Black and white patients. Pathway enrichment analysis showed downregulation of the IL-17 pathway in Black patients with localized disease. In total, five genes exhibited race-specific transcriptional differences across all stages: RAMACL, POLR2J3, POLR2J2, MUC16, and PRSS21. Logistic regression and QDA model performance indicated that these genes represent racial differences [area under the receiver operating characteristic curve (AUC): 0.863 and 0.880]. CONCLUSIONS: Significant transcriptional differences exist in CC between Black and white patients changing dynamically across disease stages, and involving genes with broad functions. Key findings include IL-17 pathway downregulation in Black patients with localized disease and a five-gene signature consistent across all stages. These findings may explain aspects of racial disparities in CC, emphasizing the need for race-specific research and treatment strategies.