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Prognostic significance of forkhead box M1 (FoxM1) expression and antitumour effect of FoxM1 inhibition in melanoma
Author(s) -
Ito Takamichi,
Kohashi Kenichi,
Yamada Yuichi,
Maekawa Akira,
Kuda Masaaki,
Furue Masutaka,
Oda Yoshinao
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12909
Subject(s) - foxm1 , melanoma , dacarbazine , cancer research , hazard ratio , medicine , thiostrepton , oncology , cell cycle , cancer , biology , confidence interval , ribosome , rna , biochemistry , gene
Aims Forkhead box M1 (FoxM1) is a transcription factor that regulates cell‐cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanoma. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma. Methods and results We investigated 60 melanoma clinical samples and a melanoma WM 266‐4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1‐overexpressing melanoma had significantly shorter survival [both for melanoma‐specific survival ( MSS ) and disease‐free survival ( DFS )] than the other patients ( P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio ( HR ): 3.96, 95% confidence interval ( CI ): 1.12–14.27, P = 0.032; HR : 3.21, 95% CI : 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using si RNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma. Conclusion We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma.