Login to Access Video or Poster Abstract: MP67-03
Sources of Funding: None

Introduction

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 differences in gene-level expression and pathway activity between black and white patients with pRCC.

Methods

The TCGA dataset was used to identify 235 (54 black, 181 white) of 290 patients with an initial diagnosis of pRCC from 2001-2013. Black and white patients were propensity matched on age, gender and pathologic TNM stage. Supervised whole genome expression analysis using the SAMSeq package in R was conducted to identify genes differentially expressed genes (FDR<0.05). Gene Set Enrichment Analysis (GSEA) to evaluate differential activity of pathways and gene sets in white and black patient groups was also conducted.

Results

There were 167 genes and 47 genes identified as overexpressed in black and white patients, respectively (FDR<0.05). Gene Set Enrichment Analysis identified 111 gene sets enriched (p<0.05) in black patients, with differences in PI3K/AKT/mTOR signaling (p<.001) and immune system pathways being the most prevalent including T cell signal transduction (p<0.001), Interferon ?/? signaling (p=.004), Interferon gamma response (p=.018), B cell antigen receptor (p=.018), IL-2 signaling (p=.015) and MHC class II antigen presentation (p=.012). PTPN20B and CRYBB2 associated with the PAK and WNT pathways were overexpressed in Black patients, respectively.

Conclusions

Distinct tumor biology between black and white patients was identified with differential activity of immune related pathways and signaling of the PI3K/AKT/mTOR pathway. While our data requires validation, these findings suggests that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, VEGFR, mTOR, MEK and PI3K inhibitors to target these pathways may improve survival in black patients with advanced pRCC.

Funding

None