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J Cancer Res Clin Oncol. 2018 Sep;144(9):1701-1709. doi: 10.1007/s00432-018-2694-5. Epub 2018 Jun 29.

FOXM1 predicts disease progression in non-muscle invasive bladder cancer.

Author information

1
Department of Hematology and Oncology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. sebastienrinal@hotmail.com.
2
Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. sebastienrinal@hotmail.com.
3
Stratifyer Molecular Pathology, Werthmannstraße 1, 50935, Cologne, Germany.
4
Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
5
Institute of Pathology, University Hospital Erlangen, Krankenhausstraße 8-10, 91054, Erlangen, Germany.
6
Department of Urology, University of Regensburg, Landshuter Str. 65, Regensburg, Germany.
7
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
8
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Abstract

PURPOSE:

The proto-oncogene forkhead box M1 (FOXM1) is associated with poor survival in many cancers. The impact of FOXM1 expression on progression-free survival (PFS) of non-muscle invasive bladder cancer (NMIBC) has not yet been investigated. The differential expression of FOXM1 between the different molecular NMIBC subtypes has further been assessed.

METHODS:

Transcript levels of FOXM1 and MKI67 were determined in 460 NMIBC patients (UROMOL cohort) by RNA-Seq and validated in silico by the Chungbuk and Lund cohort (n = 277). FOXM1 and MKI67 cutoffs were identified by the minimal p value method. Variables were evaluated by multivariable Cox regression analyses in order to identify independent predictors.

RESULTS:

FOXM1 is an independent predictor for PFS superior to current histological, clinical and molecular staging methods. Patients with high FOXM1 expression have a 6- to 8-fold higher risk of progression in multivariable analysis (p < 0.03). Highest transcript levels were found in the Class 2 and genomically unstable molecular NMIBC subtype (p < 0.03). The proto-oncogene further positively correlated with tumor grade and stage. NMIBCs with high FOXM1 expression showed a PFS advantage when treated with intravesical BCG instillation.

CONCLUSION:

FOXM1 is a highly prognostic marker for disease progression of NMIBC superior to current histological, clinical and molecular staging methods and MKI67. It is mainly expressed in the Class 2 and genomically unstable molecular bladder cancer subtypes. Its role in drug resistance development makes FOXM1 valuable biomarker for NMIBC risk stratification.

KEYWORDS:

Biomarker; Bladder cancer; FOXM1; MKI67; Molecular subtypes; Progression-free survival

PMID:
29959570
PMCID:
PMC6096766
DOI:
10.1007/s00432-018-2694-5
[Indexed for MEDLINE]
Free PMC Article

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