Rinaldetti, Sebastien and Wirtz, Ralph Markus and Worst, Thomas Stefan and Eckstein, Markus and Weiss, Cleo Aaron and Breyer, Johannes and Otto, Wolfgang and Bolenz, Christian and Hartmann, Arndt and Erben, Philipp (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). pp. 47595-47606. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)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 naive 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BREAST-CANCER; RADICAL CYSTECTOMY; HEPATOCELLULAR-CARCINOMA; REGULATES EXPRESSION; MEDIATES RESISTANCE; MOLECULAR SUBTYPES; LUMINAL SUBTYPES; GENE-EXPRESSION; POOR-PROGNOSIS; GASTRIC-CANCER; FOXM1; muscle invasive bladder cancer; KI67; subclassification; survival prediction |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 28 Feb 2019 07:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1535 |
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