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

Abstract

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 cell-related transcription factors, sex determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc), Krüppel-like 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 co-expression of SOX2, KLF4 and brachyury exhibited a significantly lower disease-specific survival rate (78.6 vs. 100%; P=0.025; χ 2 =5.033) and disease-free survival rate (60.7 vs. 90.9%; P=0.015; χ 2 =5.897) when compared with OSCC patients with high co-expression 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.

Role of Krüppel-like factor 4 and heat shock protein 27 in cancer of the larynx

“…Of note, in head and neck squamous cell carcinoma malignancies, KLF4 can exert different roles in different types. In oral squamous cell carcinoma, the expression of KLF4 increases at the early stages of the disease where it plays an oncogenic role (38). However, in our study on LSCC, opposite results were obtained.…”

Stem cell markers as a resource to predict prognosis of betel quid induced oral squamous cell carcinoma: an immunohistochemical investigation

“…[ [15][16][17][18] Etiological differences may have contributed to this result. In addition, majority of the tumors in the present study sample contained buccal mucosal cancers; while the literature quoted above have focused on tongue cancers.…”

Immunoexpression of SOX‐2 in oral leukoplakia

“…The SOX‐2 protein in cancer cells is involved in several processes such as proliferation, growth, tumorigenicity, chemoresistance, and metastasis (Liu, Lin et al., ). The elevated expression of SOX‐2 in patients with OSCC is associated with invasion and metastasis, as well as reduced survival of these patients (Yoshihama et al., ). In addition, inactivation of SOX‐2 increases the sensitivity of cells to a combination of radiation therapy and cisplatin treatment (Chou, Hu, Yu, & Yu, ).…”