Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

Author:                        

Publisher: Spandidos Publications

E-ISSN: 1792-1082|11|2|1435-1446

ISSN: 1792-1074

Source: Oncology Letters, Vol.11, Iss.2, 2016-01, pp. : 1435-1446

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Abstract

The prognosis of oral squamous cell carcinoma (OSCC) patients is affected by tumor recurrence and metastasis, and cancer stem cells are hypothesized to be involved in these processes. Thus, the aim of the present study was to determine whether the expression levels of five stem cellrelated transcription factors, sex determining region Ybox 2 (SOX2), octamerbinding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (cMyc), Krüppellike factor 4 (KLF4) and brachyury, are associated with metastasis and survival in OSCC. Immunohistochemistry was performed to analyze the expression of these proteins in biopsy specimens obtained from 108 OSCC patients. The results revealed that the expression of SOX2, Oct4, KLF4 and brachyury were significantly associated with lymph node metastasis (P=0.002, P=0.031, P=0.003 and P=0.007, respectively). In addition, the expression of KLF4 and brachyury were significantly associated with distant metastasis (P=0.014 and P=0.012, respectively). Furthermore, multivariate analysis revealed that SOX2 and KLF4 are predictive factors for lymph node metastasis [odds ratios (ORs), 4.526 and 4.851, respectively], and KLF4 is also a predictive factor for distant metastasis (OR, 9.607). In addition, OSCC patients with low coexpression of SOX2, KLF4 and brachyury exhibited a significantly lower diseasespecific survival rate (78.6 vs. 100%; P=0.025; χ2=5.033) and diseasefree survival rate (60.7 vs. 90.9%; P=0.015; χ2=5.897) when compared with OSCC patients with high coexpression of these factors. The results indicate that SOX2, KLF4 and brachyury serve important roles in tumor progression, and these transcription factors may thus represent clinically useful prognostic markers for OSCC.

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