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. 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

Sebastien Rinaldetti  1   2 , Ralph Wirtz  3 , Thomas Stefan Worst  4 , Arndt Hartmann  5 , Johannes Breyer  6 , Lars Dyrskjot  7   8 , Philipp Erben  4
Affiliations

FOXM1 predicts disease progression in non-muscle invasive bladder cancer

Sebastien Rinaldetti et al. J Cancer Res Clin Oncol. 2018 Sep.

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.

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Conflict of interest statement

All authors declare to have no COIs.

Figures

Fig. 1
Fig. 1
UROMOL cohort: a differential expression of FOXM1 based on tumor stage, grade and the 12-gene risk stratification. b Differential expression of FOXM1 based on the molecular bladder cancer subtype. c Kaplan–Meier plot for progression-free survival based on the FOXM1 risk stratification
Fig. 2
Fig. 2
Chungbuk cohort: a differential expression of FOXM1 based on tumor stage and grade. b Kaplan–Meier plots of the Chungbuk cohort for progression-free survival and overall survival associated with the FOXM1 risk stratification
Fig. 3
Fig. 3
Lund cohort: correlation of FOXM1 with clinical and molecular characteristics of the Lund cohort
Fig. 4
Fig. 4
Kaplan–Meier plot of the UROMOL cohort for progression-free survival stratified by the FOXM1 expression and BCG treatment
See this image and copyright information in PMC

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References

    1. Ark JT, Keegan KA, Barocas DA et al (2014) Incidence and predictors of understaging in patients with clinical T1 urothelial carcinoma undergoing radical cystectomy. BJU Int 113:894–899. 10.1111/bju.12245 - PMC - PubMed
    1. Babjuk M, Böhle A, Burger M et al (2017) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 71:447–461. 10.1016/j.eururo.2016.05.041 - PubMed
    1. Budczies J, Klauschen F, Sinn BV et al (2012) Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PloS One 7:e51862. 10.1371/journal.pone.0051862 - PMC - PubMed
    1. Choi W, Porten S, Kim S et al (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152–165. 10.1016/j.ccr.2014.01.009 - PMC - PubMed
    1. Contreras-Sanz A, Roberts ME, Seiler R, Black PC (2017) Recent progress with next-generation biomarkers in muscle-invasive bladder cancer. Int J Urol Off J Jpn Urol Assoc 24:7–15. 10.1111/iju.13193 - PubMed

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