Tumor Biology

, Volume 37, Issue 4, pp 5213–5223 | Cite as

FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target

  • Masaaki Kuda
  • Kenichi Kohashi
  • Yuichi Yamada
  • Akira Maekawa
  • Yoshiaki Kinoshita
  • Tetsuya Nakatsura
  • Yukihide Iwamoto
  • Tomoaki Taguchi
  • Yoshinao OdaEmail author
Original Article


The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression.


Rhabdomyosarcoma FOXM1 VEGF Prognosis 



This work was supported by JSPS KAKEN Grant Number 26462708 and Grant Number 25293088. The English used in this article was revised by KN International (

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Masaaki Kuda
    • 1
  • Kenichi Kohashi
    • 1
  • Yuichi Yamada
    • 1
  • Akira Maekawa
    • 1
  • Yoshiaki Kinoshita
    • 2
  • Tetsuya Nakatsura
    • 4
  • Yukihide Iwamoto
    • 3
  • Tomoaki Taguchi
    • 2
  • Yoshinao Oda
    • 1
    Email author
  1. 1.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Pediatric Surgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Orthopedic Surgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Division of Cancer ImmunotherapyNational Cancer Center Hospital EastKashiwaJapan

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