MP06-02 NON-MUSCLE-INVASIVE MICROPAPILLARY BLADDER CANCER HAS A DISTINCT LNCRNA PROFILE ASSOCIATED WITH UNFAVORABLE PROGNOSIS

Abstract

You have accessJournal of UrologyCME1 May 2022MP06-02 NON-MUSCLE-INVASIVE MICROPAPILLARY BLADDER CANCER HAS A DISTINCT LNCRNA PROFILE ASSOCIATED WITH UNFAVORABLE PROGNOSIS Joep de Jong, Begoña Valderrama, Julia Perera, Nuria Juanpere, Paloma Cejas, Henry Long, Mar Alba, Ewan Gibb, and Joaquim Bellmunt Joep de JongJoep de Jong More articles by this author , Begoña ValderramaBegoña Valderrama More articles by this author , Julia PereraJulia Perera More articles by this author , Nuria JuanpereNuria Juanpere More articles by this author , Paloma CejasPaloma Cejas More articles by this author , Henry LongHenry Long More articles by this author , Mar AlbaMar Alba More articles by this author , Ewan GibbEwan Gibb More articles by this author , and Joaquim BellmuntJoaquim Bellmunt More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002523.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Molecular subtyping of bladder cancer has revealed luminal tumors generally have a more favorable prognosis. However, some aggressive forms of variant histology, including micropapillary, are often classified luminal. In previous work, we found long non-coding RNA (lncRNA) expression profiles could identify a subgroup of luminal bladder tumors with less aggressive biology and better outcomes. In the present study, we aimed to investigate whether lncRNA expression profiles could identify high-grade T1 micropapillary bladder cancer with differential outcome. METHODS: LncRNAs were quantified from RNA-seq data from a HG T1 bladder cancer cohort that was enriched for primary micropapillary cases (15/84). Unsupervised consensus clustering of variant lncRNAs identified a three-cluster solution, which was characterized using a panel of micropapillary-associated biomarkers, molecular subtypes, gene signatures and survival analysis. A single-sample genomic signature was trained using lasso-penalized logistic regression to classify micropapillary-like gene-expression, as characterized by lncRNA clustering. The genomic classifier (GC) was tested on luminal tumors derived from the TCGA cohort (N=202). Primary endpoints were overall, progression-free and high-grade recurrence-free survival. RESULTS: Primary micropapillary HGT1 showed decreased FGFR3, SHH and p53 pathway activity relative to tumors with conventional urothelial carcinoma. Many bladder cancer-associated lncRNAs were downregulated in micropapillary tumors, including UCA1, LINC00152, and MALAT1. Unsupervised consensus clustering resulted in a lncRNA cluster (LC1) with worse prognosis that was enriched for primary micropapillary histology and the Luminal Unstable (LumU) molecular subtype. Interestingly, LC1 appeared to better identify aggressive HG T1 disease, compared to stratifying outcomes using primary histologic characteristics. A signature trained to identify LC1 cases showed good performance in the testing cohort, identifying seven cases with significantly worse survival (p<0.001). CONCLUSIONS: Using the lncRNA transcriptome we identified a subgroup of aggressive HGT1 bladder cancer that was enriched with micropapillary histology. These data suggest that lncRNAs can facilitate the identification of aggressive micropapillary-like tumors, potentially improving patient management. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e77 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joep de Jong More articles by this author Begoña Valderrama More articles by this author Julia Perera More articles by this author Nuria Juanpere More articles by this author Paloma Cejas More articles by this author Henry Long More articles by this author Mar Alba More articles by this author Ewan Gibb More articles by this author Joaquim Bellmunt More articles by this author Expand All Advertisement PDF DownloadLoading ...