FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

Sikic, Danijel and Eckstein, Markus and Wirtz, Ralph M. and Jarczyk, Jonas and Worst, Thomas S. and Porubsky, Stefan and Keck, Bastian and Kunath, Frank and Weyerer, Veronika and Breyer, Johannes and Otto, Wolfgang and Rinaldetti, Sebastien and Bolenz, Christian and Hartmann, Arndt and Wullich, Bernd and Erben, Philipp (2020) FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy. JOURNAL OF CLINICAL MEDICINE, 9 (4): 994. ISSN , 2077-0383

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Abstract

It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 (p = 0.0048) and KRT20 (p = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS (p = 0.0333) and RFS (p = 0.0310). FOXA1 expression (AUC = 0.79; p = 0.0007) was closest to the combined marker expression (AUC = 0.79; p = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC.

Item Type: Article
Uncontrolled Keywords: MESSENGER-RNA EXPRESSION; UROTHELIAL CARCINOMA; LUMINAL SUBTYPES; RECURRENCE; CONSENSUS; TAXONOMY; BASAL; FOXA1; GATA3; KRT20; molecular markers; mRNA; muscle-invasive bladder cancer; PCR; urothelial carcinoma
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Urologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Mar 2021 04:57
Last Modified: 29 Mar 2021 04:57
URI: https://pred.uni-regensburg.de/id/eprint/44798

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