J Cancer 2019; 10(3):749-756. doi:10.7150/jca.28099

Research Paper

High FOXM1 expression is a prognostic marker for poor clinical outcomes in prostate cancer

Mee Young Kim1,2, Ae Ryang Jung1,2, Ga Eun Kim1,2, Jonghyup Yang1, U-Syn Ha1,2, Sung-Hoo Hong1,2, Yeong Jin Choi2,3, Mi Hyoung Moon4, Sae Woong Kim1, Ji Youl Lee1,2, Yong Hyun Park1,2,✉

1. Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
2. Cancer Research Institute, College of Medicine, The Catholic University of Korea
3. Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
4. Department of Thoracic and Cardiovascular Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea

Abstract

Purpose: We aimed to investigate the expression of FOXM1 and to determine the relationships between FOXM1 expression and clinicopathologic characteristics in patients with PCa. Furthermore, we reconfirmed the prognostic impact of FOXM1 in different cohorts using already published data.

Patients and Methods: Formalin-fixed, paraffin-embedded tissues were collected from patients with low- (n=17), intermediate- (n=36), and high-risk (n=29) disease, from patients with CRPC (n=2) and from patients with BPH (n=28). To analyze FOXM1 expression, we performed IHC analyses. Also, we analyzed gene expression data from cBioPortal to evaluate the associations between FOXM1 alteration and prognosis of PCa.

Results: FOXM1 expression measured using Allred score differed between patients with BPH, and low-, intermediate-, and high-risk PCa (0.3, 1.5, 4.8, and 6.2, respectively; p<0.001). Patients with high FOXM1 expression had higher preoperative PSA levels (p=0.023), more advanced tumor stages (p=0.047), and higher pathologic Gleason score (p<0.001) than those with low FOXM1 expression. ROC curve analysis indicated that FOXM1 expression was a useful marker for discriminating PCa from BPH (AUC 0.851, 95% CI 0.783-0.920) and for discriminating high-risk PCa from low- and intermediate-risk PCa (AUC 0.807, 95% CI 0.719-0.894). In multivariate analyses, high FOXM1 expression was an independent predictor of BCR. Finally, in the TCGA dataset, FOXM1 alteration was associated with poor overall (p=4.521e-4) and disease-free survival (p=0.0108).

Conclusions: In patients with PCa, high FOXM1 expression was associated with advanced tumor stages, high Gleason score, and poor prognosis. These data suggest a role of FOXM1 in biologically and clinically aggressive PCa.

Keywords: Prostatic Neoplasms, Forkhead Box protein M1, Biomarkers

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How to cite this article:
Kim MY, Jung AR, Kim GE, Yang J, Ha US, Hong SH, Choi YJ, Moon MH, Kim SW, Lee JY, Park YH. High FOXM1 expression is a prognostic marker for poor clinical outcomes in prostate cancer. J Cancer 2019; 10(3):749-756. doi:10.7150/jca.28099. Available from http://www.jcancer.org/v10p0749.htm