Expression Analysis of Same-Patient Metachronous and Synchronous Upper Tract and Bladder Urothelial Carcinoma

Firas G. Petros, Woonyoung Choi, Yuan Qi, Tyler Moss, Roger Li, Xiaoping Su, Charles C. Guo, Bogdan Czerniak, Colin Dinney, David J. McConkey, Surena F. Matin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Purpose:We compared upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) in same-patient metachronous UTUC and synchronous UTUC and BUC using next-generation sequencing.Materials and Methods:Consecutive untreated same-patient samples of UTUC and BUC were macrodissected from unstained formalin-fixed, paraffin-embedded slides after quality control. Samples were divided into 4 groups: 1) UTUC-metachronous BUC, 2) BUC-metachronous UTUC, 3) synchronous UTUC-BUC, 4) UTUC without BUC. Exclusions were inadequate clinical data or histological tumor purity <30%. Whole transcriptome RNA sequencing was performed. After quality assessment, gene expression clusters using unsupervised hierarchical consensus clustering and correlation with pertinent clinicopathologic variables, a prior RNASeq data set and other published data were performed.Results:RNAseq was performed on 95 samples (UTUC=61, BUC=34) from 40 untreated patients. Unsupervised consensus clustering segregated the tumors into 2 clusters that were enriched with BASE47 basal-like or luminal-like gene expression. Almost two-thirds (61.9%) of Group 2 tumors were basal-like, while the majority of Groups 1, 3, 4 (80.6%, 70.0% and 69.6%, respectively) were luminal-like (p=0.017). Further analyses revealed that the differences in basal-like and luminal-like gene expression were associated with differential fibroblast and immune cell gene expression signatures. In all, 87.5% of metachronous tumors maintained subtype membership.Conclusions:Gene expression analysis of same-patient metachronous UTUC-BUC suggests that the majority of mUTUC developing after BUC appear more basal-like, while synchronous and initial UTUC tumors appear luminal-like. Metachronous tumors largely maintain molecular subtype membership of the initial tumor regardless of chronologic development or anatomical origin.

Original languageEnglish (US)
Pages (from-to)548-557
Number of pages10
JournalJournal of Urology
Volume206
Issue number3
DOIs
StatePublished - Sep 1 2021

Keywords

  • RNA
  • genome
  • ureteral neoplasms
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource

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