PD07-07 MOLECULAR SUBTYPING OF >80,000 PROSTATE CANCER TRANSCRIPTOMES IDENTIFIES FOUR CLASSES WITH DISTINCT BIOLOGICAL AND CLINICAL CHARACTERISTICS WITH IMPLICATIONS FOR TARGETED THERAPIES

Abstract

You have accessJournal of UrologyCME1 May 2022PD07-07 MOLECULAR SUBTYPING OF >80,000 PROSTATE CANCER TRANSCRIPTOMES IDENTIFIES FOUR CLASSES WITH DISTINCT BIOLOGICAL AND CLINICAL CHARACTERISTICS WITH IMPLICATIONS FOR TARGETED THERAPIES Adam Weiner, Yang Liu, Ashley Ross, Felix Feng, Phuoc Tran, Nicholas Zaorsky, Angela Jia, Xin Zhao, Alex Hakansson, Vinnie Liu, James Proudfoot, Ewan Gibb, Elai Davicioni, Daniel Spratt, and Edward Schaeffer Adam WeinerAdam Weiner More articles by this author , Yang LiuYang Liu More articles by this author , Ashley RossAshley Ross More articles by this author , Felix FengFelix Feng More articles by this author , Phuoc TranPhuoc Tran More articles by this author , Nicholas ZaorskyNicholas Zaorsky More articles by this author , Angela JiaAngela Jia More articles by this author , Xin ZhaoXin Zhao More articles by this author , Alex HakanssonAlex Hakansson More articles by this author , Vinnie LiuVinnie Liu More articles by this author , James ProudfootJames Proudfoot More articles by this author , Ewan GibbEwan Gibb More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Daniel SprattDaniel Spratt More articles by this author , and Edward SchaefferEdward Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002526.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We used molecular subtyping to characterize the largest prostate cancer transcriptome database to understand the tumor behavior and help guide treatment decision making. METHODS: Whole transcriptome analyses was performed on de-identified tumor samples from biopsies or radical prostatectomy from the clinical use of the Decipher prostate genomic classifier (Decipher Biosciences, San Diego, CA; n=32,000, training cohort, n=48,703, testing cohort). We grouped these patients based on expression patterns of a curated panel of signatures and biomarkers relevant to systemic therapies for prostate cancer (n=21), from which we identified 4 clusters with distinct biological characteristics. A multinomial logistic regression was trained to reproduce the clusters as a single sample classifier. RESULTS: Luminal-Differentiating (LD) tumors had the highest AR-activity scores, upregulation of canonical AR transcriptional targets (i.e., PSA and PSMA; Fig). Luminal Proliferating (LP) tumors had the highest expression of AR, and cell proliferation genes (e.g., MKI67 and TOP2A) and pathways. Basal Immune (BI) tumors possessed significant immune infiltration and T-effector cell activity and low levels of immune suppressor signatures. Basal Neuroendocrine (BN) tumors were characterized by low AR-activity expression, low immune infiltration, and enrichment with neuronal gene expression. LP and BI tumors tended to possess more aggressive clinical characteristics: high proportions of grade group 4-5, node positive disease (BI only), and high Decipher score. In a cohort of patients treated with radical prostatectomy (n=855), patients with LD tumors experienced longer metastasis-free survival compared to LP (HR=3.56 [1.83-6.93]), BI (HR=2.55 [1.29-5.01]) and BN (HR=3.30 [1.03-10.61]) with Cox regression adjusting for age, PSA, stage and Gleason score. CONCLUSIONS: This molecular subtyping model for prostate cancer, derived from the largest reported transcriptome analysis of primary tumors segments tumors by relevant biological processes with potential implications for targeting systemic therapies. Source of Funding: Decipher Biosciences © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e101 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adam Weiner More articles by this author Yang Liu More articles by this author Ashley Ross More articles by this author Felix Feng More articles by this author Phuoc Tran More articles by this author Nicholas Zaorsky More articles by this author Angela Jia More articles by this author Xin Zhao More articles by this author Alex Hakansson More articles by this author Vinnie Liu More articles by this author James Proudfoot More articles by this author Ewan Gibb More articles by this author Elai Davicioni More articles by this author Daniel Spratt More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement PDF DownloadLoading ...