Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma

Abstract

Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assessed gene-level expression, somatic mutation and pathway differences between 58 black and 58 white patients with pRCC propensity matched on age, gender and pathologic T stage. Distinct tumor biology with differential expression patterns were observed in black vs. white patients with pRCC. Specifically, significance analysis of microarrays was applied to TCGA gene expression data and identified 163 genes and 120 genes overexpressed in black and white patients, respectively (FDR q<0.05). Gene Set Enrichment Analysis identified 62 gene sets enriched (p<0.10) in blacks. Enrichment of immune immune system pathways were noted in black patients. These included the B cell receptor signaling pathway, the NOD-like receptor signaling pathway and genes involved in defensins. The VEGF pathway was also more significant in black patients. CRYBB2, a gene associated with the WNT pathway was overexpressed in Black patients. While our data requires validation, these findings suggest that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, and VEGFR inhibitors to target these pathways may improve survival in black patients with advanced pRCC.

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

“…Human genetics contribute to the propensity and severity of diseases 21,[30][31][32][33][34][35][36][37] . Sometimes the contribution is straightforward; a single allele variation found in Ashkenazi Jews, causes the vast majority of Tay-Sachs disease 36 .…”

A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer

“…Thus, this gene has successfully been used as a classifier to distinguish between racial groups. Further, higher CRYβB2 expression has been correlated to poorer outcome in cancer, regardless of race [7, 11, 12, 14–16]. Even with these findings, no study has demonstrated a functional role for CRYβB2 in cancers.…”

Comprehensive subgroup analyses of survival outcomes between clear cell renal cell adenocarcinoma and papillary renal cell adenocarcinoma

“…15 Paulucci et al demonstrated different immune responses to cancer between black and white patients. 16 Thus, there exists the possibility that genomic or molecular differences between NHB and NHW patients might cause distinct survival outcomes. This conclusion can inspire further explorations.…”