PD01-10 WHOLE TRANSCRIPTOME SEQUENCING OF CLEAR CELL RENAL CELL CARCINOMA REVEALS A MULTIGENE EXPRESSION PROGNOSTIC SIGNATURE

Abstract

You have accessJournal of UrologyCME1 May 2022PD01-10 WHOLE TRANSCRIPTOME SEQUENCING OF CLEAR CELL RENAL CELL CARCINOMA REVEALS A MULTIGENE EXPRESSION PROGNOSTIC SIGNATURE Srinivas Nallandhighal, Rohit Mehra, Marcin Cieslik, Amy Kasputis, Brittney Cotta, Todd Morgan, and Simpa Salami Srinivas NallandhighalSrinivas Nallandhighal More articles by this author , Rohit MehraRohit Mehra More articles by this author , Marcin CieslikMarcin Cieslik More articles by this author , Amy KasputisAmy Kasputis More articles by this author , Brittney CottaBrittney Cotta More articles by this author , Todd MorganTodd Morgan More articles by this author , and Simpa SalamiSimpa Salami More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002516.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is a critical need to develop prognostic biomarkers to improve the management of patients with clear cell renal cell carcinoma (ccRCC). This study aims to develop and validate gene expression-based biomarkers associated with recurrent disease to facilitate risk-stratification of ccRCC. METHODS: We retrospectively identified 110 patients who underwent radical nephrectomy for localized ccRCC. Patients who recurred were matched based on grade/stage to patients without recurrence. RNA next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded (FFPE) tissue using whole-transcriptome sequencing on the illumina platform. We developed a gene signature to predict recurrence/progression-free survival (PFS) using a 15-fold lasso and elastic-net regularized linear Cox model. We derived Myriad Prolaris™ commercially available 31-gene cell cycle proliferation (mxCCP) score using RNA-seq data for each patient. Validation datasets were assembled: dataset #1 - The Cancer Genome Atlas ccRCC (TCGA, n= 382) and dataset #2 [Seishi Ogawa Japanese (n=87), International Cancer Genome Consortium (ICGC; n=81), GSE22541 (n=20) and Clinical Proteomics Tumor Analysis Consortium (CPTAC; n=91)]. Kaplan-Meier (KM) curves and multivariate Cox proportional hazard testing were then used to validate the independent prognostic impact of the gene signature on PFS and disease specific survival (DSS). RESULTS: After quality control, the training cohort comprised 50 patients with recurrence and 41 patients without, with a median follow-up 26 and 36 months, respectively. There were no significant differences between age, sex, grade, and stage between groups (all p > 0.05). We developed a 15-gene signature which was the only variable independently associated with worse PFS and DSS (PFS: HR=11.08, CI=4.9-25.1; DSS: HR=9.67, CI=3.4-27.7), adjusting for clinical-pathologic variables and mxCCP score. The 15-gene signature was also independently associated with worse PFS and DSS in both validation datasets [Validation #1 (n=382), PFS: HR=2.6, CI=1.6-4.3; DSS: HR=3; CI=1.4-6.1 and Validation #2 (n=279), PFS: HR=1.6, CI=0.7-3.6; DSS: HR=3.1; CI=1.5-6.4] adjusting for clinical-pathologic variables and mxCCP score. CONCLUSIONS: We developed and validated a novel 15-gene prognostic signature to improve risk stratification of patients with ccRCC. This signature has the potential to facilitate optimal treatment allocation and may lead to the development of novel therapeutic targets. Source of Funding: National Comprehensive Cancer Network © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e33 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Srinivas Nallandhighal More articles by this author Rohit Mehra More articles by this author Marcin Cieslik More articles by this author Amy Kasputis More articles by this author Brittney Cotta More articles by this author Todd Morgan More articles by this author Simpa Salami More articles by this author Expand All Advertisement PDF DownloadLoading ...