Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas

Akira Maekawa, Kenichi Kohashi, Masaaki Kuda, Kunio Iura, Takeaki Ishii, Makoto Endo, Tetsuya Nakatsura, Yukihide Iwamoto, Yoshinao Oda

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Synovial sarcoma (SS) is a soft tissue sarcoma of unknown histogenesis. Most metastatic or unresectable cases are incurable. Novel antitumor agents and precise prognostication are needed for SS patients. The protein forkhead box M1 (FOXM1), which belongs to the FOX family of transcription factors, is considered to be an independent predictor of poor survival in many cancers and sarcomas, but the prognostic implications and oncogenic roles of FOXM1 in SS are poorly understood. Here we examined the correlation between FOXM1 expression and clinicopathologic and prognostic factors, and we investigated the efficacy of FOXM1 target therapy in SS cases. Methods: Immunohistochemical study of 106 tumor specimens was conducted to evaluate their immunohistochemical expression of FOXM1. An in vitro study examined the antitumor effect of the FOXM1 inhibitor thiostrepton and small interference RNA (siRNA) on two SS cell lines. We also assessed the efficacy of the combined use of doxorubicin (DOX) and thiostrepton. Results: Univariate and multivariate analyses revealed that FOXM1 expression was associated with poor prognosis in SS. The cDNA microarray analysis using clinical samples revealed that the expression of cell cycle-associated genes was correlated with FOXM1 expression. FOXM1 inhibition by thiostrepton showed significant antitumor activity on the SS cell lines in vitro. FOXM1 interruption by siRNA increased the chemosensitivity for DOX in both SS cell lines. Conclusion: FOXM1 expression is a novel biomarker, and its inhibition is a potential treatment option for SS.

Original languageEnglish
Article number511
JournalBMC Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - Jul 20 2016

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Synovial Sarcoma
Thiostrepton
RNA Interference
Cell Line
Sarcoma
Doxorubicin
cdc Genes
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Antineoplastic Agents
Neoplasms
Transcription Factors
Multivariate Analysis
Biomarkers

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas. / Maekawa, Akira; Kohashi, Kenichi; Kuda, Masaaki; Iura, Kunio; Ishii, Takeaki; Endo, Makoto; Nakatsura, Tetsuya; Iwamoto, Yukihide; Oda, Yoshinao.

In: BMC Cancer, Vol. 16, No. 1, 511, 20.07.2016.

Research output: Contribution to journalArticle

Maekawa, Akira ; Kohashi, Kenichi ; Kuda, Masaaki ; Iura, Kunio ; Ishii, Takeaki ; Endo, Makoto ; Nakatsura, Tetsuya ; Iwamoto, Yukihide ; Oda, Yoshinao. / Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas. In: BMC Cancer. 2016 ; Vol. 16, No. 1.
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