PD39-06 POOR RESPONSE TO IMMUNOTHERAPY IS ASSOCIATED WITH HIGH EXPRESSION OF A NOVEL EPIDERMAL GROWTH FACTOR RECEPTOR SPLICE VARIANT IN PATIENTS WITH RENAL CELL CARCINOMA

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You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) II (PD39)1 Apr 2020PD39-06 POOR RESPONSE TO IMMUNOTHERAPY IS ASSOCIATED WITH HIGH EXPRESSION OF A NOVEL EPIDERMAL GROWTH FACTOR RECEPTOR SPLICE VARIANT IN PATIENTS WITH RENAL CELL CARCINOMA Ali Hajiran*, Youngchul Kim, Saif Zaman, Thushara Madanyake, Timothy Robinson, Shayan Falasiri, Philippe Spiess, Manish Kohli, Theresa Boyle, James Mulé, Jamie Teer, and Brandon Manley Ali Hajiran*Ali Hajiran* More articles by this author , Youngchul KimYoungchul Kim More articles by this author , Saif ZamanSaif Zaman More articles by this author , Thushara MadanyakeThushara Madanyake More articles by this author , Timothy RobinsonTimothy Robinson More articles by this author , Shayan FalasiriShayan Falasiri More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Manish KohliManish Kohli More articles by this author , Theresa BoyleTheresa Boyle More articles by this author , James MuléJames Mulé More articles by this author , Jamie TeerJamie Teer More articles by this author , and Brandon ManleyBrandon Manley More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000918.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Epidermal growth factor receptor (EGFR) is a widely activated oncogene associated with several types of cancer. We identified a novel aberrant EGFR splice variant (EGFR-20-CTF) with specific expression in patients with clear cell renal cell carcinoma (ccRCC). The purpose of this study was to correlate EGFR-20-CTF expression with response to immunotherapy. METHODS: The tumors of 88 patients with ccRCC underwent RNA sequencing and characterization of EGFR-20-CTF. Nineteen patients had received immunotherapy. Patients were divided into 3 tertiles based on levels of EGFR-20-CTF expression. The time from first immunotherapy treatment to death was measured for each patient. Log-rank tests were used to compare survival between groups. Gene set enrichment analysis (GSEA) was also performed. RESULTS: EGFR-20-CTF was identified in 76.1% of ccRCC tumors. Patients with the highest levels of EFR-20-CTF expression had significantly worse survival at 48 months compared to patients with low EGFR-20-CTF (p = 0.036). The average survival in patients with high EGFR-20-CTF expression was < 16 months. GSEA showed that EGFR-20-CTF correlated with a significant decrease in expression of gene sets related to immune response including the HALLMARK inflammatory response, IL-2 signaling, and INF gamma response (all FDR q-val < 0.001). CONCLUSIONS: EGFR-20-CTF occurs frequently in patients with ccRCC and is enriched in patients who had a poor response to immunotherapy. The presence of the EGFR-20-CTF was associated with a global decrease in expression of several gene sets related to immune response, which could account for the decreased response to immunotherapy observed in these patients. This previously unrecognized splice variant presents a possible marker of resistance and will need prospective validation. Source of Funding: Urology Care Foundation Research Scholar Award Program; Society for Urologic Oncology © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e810-e811 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ali Hajiran* More articles by this author Youngchul Kim More articles by this author Saif Zaman More articles by this author Thushara Madanyake More articles by this author Timothy Robinson More articles by this author Shayan Falasiri More articles by this author Philippe Spiess More articles by this author Manish Kohli More articles by this author Theresa Boyle More articles by this author James Mulé More articles by this author Jamie Teer More articles by this author Brandon Manley More articles by this author Expand All Advertisement PDF downloadLoading ...