MP47-04 VALIDATION OF A 22-GENE EPITHELIAL-MESENCHYMAL TRANSITION (EMT) PROGNOSTIC SIGNATURE IN CLEAR CELL RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyCME1 May 2022MP47-04 VALIDATION OF A 22-GENE EPITHELIAL-MESENCHYMAL TRANSITION (EMT) PROGNOSTIC SIGNATURE IN CLEAR CELL RENAL CELL CARCINOMA Brittney Cotta, Srinivas Nallandhighal, Judith Stangl-Kremser, Trinh Pham, Jeffrey Tosoian, Kathryn Marchetti, Joel Berends, Mahir Maruf, Scott Tomlins, Todd Morgan, Ganesh Palapattu, Eman Abdulfatah, Aaron Udager, and Simpa Salami Brittney CottaBrittney Cotta More articles by this author , Srinivas NallandhighalSrinivas Nallandhighal More articles by this author , Judith Stangl-KremserJudith Stangl-Kremser More articles by this author , Trinh PhamTrinh Pham More articles by this author , Jeffrey TosoianJeffrey Tosoian More articles by this author , Kathryn MarchettiKathryn Marchetti More articles by this author , Joel BerendsJoel Berends More articles by this author , Mahir MarufMahir Maruf More articles by this author , Scott TomlinsScott Tomlins More articles by this author , Todd MorganTodd Morgan More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , Eman AbdulfatahEman Abdulfatah More articles by this author , Aaron UdagerAaron Udager More articles by this author , and Simpa SalamiSimpa Salami More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002618.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current predictors of metastatic progression after radical nephrectomy for localized clear cell renal cell carcinoma (ccRCC) include clinicopathologic features such as tumor stage and grade. The addition of molecular tumor characteristics in a prognostic score may improve risk stratification and patient selection for enhanced follow up strategies or adjuvant therapies. METHODS: We retrospectively identified consecutive patients with ccRCC who underwent radical nephrectomy (RNx) for localized disease. Those who developed metastasis were identified. Whole-transcriptome mRNA sequencing of primary tumors was performed followed by gene set enrichment analysis (GSEA) for the most significant cancer hallmark pathways enriched in patients who did or did not develop metastasis. For each patient, the 22-gene epithelial mesenchymal transition (EMT) score was calculated (high vs. low), using cut-offs from a prior study using TCGA data. The prognostic impact of the EMT score was evaluated by performing multivariable cox-proportional hazard testing and Kaplan-Meier (KM) survival analysis. RESULTS: We analyzed 82 patients with median age 62 years and median tumor size 6 ±2.9 cm. The median time to metastasis after radical nephrectomy for patients who developed metastasis (n=12) was 18.2 months and median follow up 31.1 months for patients who did not develop metastasis (n=70). We observed a significant enrichment of EMT, myogenesis, inflammatory response and hypoxia hallmark pathways in patients with metastasis vs. those without metastasis. Kaplan-Meier survival analysis showed a significant decrease in metastasis-free survival in patients with a high EMT score (p=0.018). Multivariable analysis controlling for relevant clinicopathologic features such as age, sex, tumor size, tumor stage etc. revealed high EMT score to be significantly associated with development of metastasis [hazard ratio (HR) 7.2; 95% CI 1.15-44.8; p=0.035]. CONCLUSIONS: We validated a prognostic 22-gene epithelial mesenchymal transition (EMT) score in patients treated with radical nephrectomy for localized ccRCC. Pending further studies, the EMT score may improve risk stratification and select patients for adjuvant therapy. Source of Funding: UM-Peking University Joint Institute, NCI T32 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e810 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brittney Cotta More articles by this author Srinivas Nallandhighal More articles by this author Judith Stangl-Kremser More articles by this author Trinh Pham More articles by this author Jeffrey Tosoian More articles by this author Kathryn Marchetti More articles by this author Joel Berends More articles by this author Mahir Maruf More articles by this author Scott Tomlins More articles by this author Todd Morgan More articles by this author Ganesh Palapattu More articles by this author Eman Abdulfatah More articles by this author Aaron Udager More articles by this author Simpa Salami More articles by this author Expand All Advertisement PDF DownloadLoading ...