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

被引：22

作者：

Maekawa, Akira ^{[1
]}

Kohashi, Kenichi ^{[1
]}

Kuda, Masaaki ^{[1
]}

Iura, Kunio ^{[1
]}

Ishii, Takeaki ^{[1
]}

Endo, Makoto ^{[2
]}

Nakatsura, Tetsuya ^{[3
]}

Iwamoto, Yukihide ^{[2
]}

Oda, Yoshinao ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Orthoped Surg, Fukuoka, Japan

[3] Natl Canc Ctr Hosp East, Div Canc Immunotherapy, Kashiwa, Chiba, Japan

来源：

BMC CANCER | 2016年 / 16卷

基金：

日本学术振兴会;

关键词：

Forkhead box M1 (FOXM1); Synovial sarcoma; Thiostrepton; FORKHEAD BOX M1; TRANSCRIPTION FACTOR FOXM1; POOR-PROGNOSIS; SIGNALING PATHWAY; CELL-LINE; BINDING; CANCER; GENES; PROLIFERATION; PROGRESSION;

D O I：

10.1186/s12885-016-2542-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：12

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