FOXM1 predicts overall and disease specific survival in muscle-invasive urothelial carcinoma and presents a differential expression between bladder cancer subtypes

Rinaldetti S, Wirtz RM, Worst TS, Eckstein M, Weiss CA, Breyer J, Otto W, Bolenz C, Hartmann A, Erben P (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Oncotarget Impact Journals

Book Volume: 8

Pages Range: 47595-47606

Journal Issue: 29

DOI: 10.18632/oncotarget.17394

Abstract

Forkhead box M1 (FOXM1) is a late cell cycle gene that plays a crucial role in carcinogenesis and chemotherapeutic drug resistance. In this study, the impact of FOXM1 expression on patient outcome was investigated for the first time in formalin fixed and paraffin embedded (FFPE) samples of chemotherapy naïve muscle-invasive bladder cancer (MIBC) patients. Expression analyses were performed on the Mannheim cohort (n=84) and validated on the independent Chungbuk cohort (n=61). In a Cox' proportional hazards model, a distinct FOXM1 expression cut-off dividing both cohorts in a 'high-risk' and 'low-risk' group has been determined. Multivariate analyses showed that FOXM1 is an independent risk factor for outcome prediction superior to the TNM system. The FOXM1 'high-risk' group had a 4- to 7-fold increased risk of death (p<0.03) and presented further an overexpression of MKI67. Recent studies showed that MIBCs can be subclassified in breast cancer-like subtypes: basal, luminal and p53-like. Here we demonstrated that FOXM1 was differentially expressed between MIBC subtypes concordant to its subtype specific expression in breast cancer. Since the proto-oncogene FOXM1 is known to play an important role in cisplatin resistance and to be a promising drug target, this study supports FOXM1 as a crucial biomarker in the personalization of MIBC therapy and urges prospective translational studies.

Authors with CRIS profile

Markus Eckstein Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universität Ulm DE Germany (DE) Universität Regensburg DE Germany (DE) STRATIFYER Molecular Pathology GmbH DE Germany (DE)

How to cite

APA:

Rinaldetti, S., Wirtz, R.M., Worst, T.S., Eckstein, M., Weiss, C.A., Breyer, J.,... Erben, P. (2017). FOXM1 predicts overall and disease specific survival in muscle-invasive urothelial carcinoma and presents a differential expression between bladder cancer subtypes. Oncotarget, 8(29), 47595-47606. https://doi.org/10.18632/oncotarget.17394

MLA:

Rinaldetti, Sebastien, et al. "FOXM1 predicts overall and disease specific survival in muscle-invasive urothelial carcinoma and presents a differential expression between bladder cancer subtypes." Oncotarget 8.29 (2017): 47595-47606.

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