High expression of FOXM1 is a potential prognostic marker for oral squamous cell carcinoma patients treated with docetaxel-containing regimens

Background

Forkhead box protein M1 (FOXM1) is an oncoprotein that regulates cell growth and differentiation, angiogenesis, apoptosis and aging; and it is reported to play an important role in progression and drug sensitivity of various cancers. The purpose of this study was to determine whether FOXM1 expression could be a useful prognostic factor for oral squamous cell carcinoma (OSCC).

Methods

FOXM1 expression was investigated by immunohistochemistry in tissue samples of 56 OSCC patients treated with docetaxel (DOC)-containing regimens. In this study, we investigated the relationship between FOXM1 expression and clinicopathological features of OSCC, as well as the prognosis of above patients. Moreover, we examined the expression of FOXM1 in DOC-resistant human tongue carcinoma cell lines (HSC2/DOC, HSC3/DOC and HSC4/DOC) in vitro. We established these DOC-resistant cell lines by exposing HSC2, HSC3 and HSC4 parental cells to increasing concentrations of DOC over approximately two years.

Results

FOXM1 was detected both in nucleus and cytoplasm of OSCC tumor cells. FOXM1 expression in tumor tissues was significantly correlated with N classification (P = 0.0395), stage (P = 0.004), therapeutic efficacy (P = 0.0113) and outcome of patient (P = 0.0134); although there was no correlation between FOXM1 expression and patient's gender, age or T classification. Moreover, high expression of FOXM1 in tumor cells was associated with shorter overall survival (OS, P = 0.0257). Multivariate analysis also revealed that high expression of FOXM1 was a predictor of reduced survival (P = 0.0327). Additionally, DOC-resistant OSCC cell lines showed significantly higher expression of FOXM1 compared to the parental cell lines in vitro.

Conclusions

These findings suggest that high expression of FOXM1 in OSCC tumors is correlated with DOC resistance, as well as poor therapeutic effects and worse clinical outcomes in OSCC patients treated with DOC -containing regimen. Therefore, FOXM1 might have prognostic significance in oral squamous cell carcinoma patients.

Clinical trial identification

Legal entity responsible for the study

Yamaguchi Unversity Graduate School of medicine

Funding

Grant-in-Aid from the Japanese Ministry of Education, Science and Culture

Disclosure

All authors have declared no conflicts of interest.