Mp67-03 Differential Activity of Immune System Pathways and the Pi3k/akt/mtor Pathway in Black and White Patients With Papillary Renal Cell Carcinoma
Year: 2017
Type: article
Abstract: You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging II1 Apr 2017MP67-03 DIFFERENTIAL ACTIVITY OF IMMUNE SYSTEM PATHWAYS AND THE PI3K/AKT/MTOR PATHWAY IN BLACK AND WHITE PATIENTS WITH PAPILLARY RENAL CELL CARCINOMA David Paulucci, John Sfakianos, Anders Skanderup, Kathleen Kan, Che-Kai Tsao, Matthew Galsky, A Ari Hakimi, and Ketan Badani David PaulucciDavid Paulucci More articles by this author , John SfakianosJohn Sfakianos More articles by this author , Anders SkanderupAnders Skanderup More articles by this author , Kathleen KanKathleen Kan More articles by this author , Che-Kai TsaoChe-Kai Tsao More articles by this author , Matthew GalskyMatthew Galsky More articles by this author , A Ari HakimiA Ari Hakimi More articles by this author , and Ketan BadaniKetan Badani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2039AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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 a/ß 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. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e871-e872 Advertisement Copyright & Permissions© 2017MetricsAuthor Information David Paulucci More articles by this author John Sfakianos More articles by this author Anders Skanderup More articles by this author Kathleen Kan More articles by this author Che-Kai Tsao More articles by this author Matthew Galsky More articles by this author A Ari Hakimi More articles by this author Ketan Badani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2604565059