title: Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma.
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; χ2=5.033) and disease-free survival rate (60.7 vs. 90.9%; P=0.015; χ2=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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Yoshihama
authors.affiliation: Department of Maxillofacial Diagnostic and Surgical Science, Graduate School of Dental Science, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Koujiro
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Imajyo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Mine
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Hiyake
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Naonari
authors.initials: N
authors.lastname: Akimoto
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Chigita
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kumamaru
authors.affiliation: Department of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kiyoshima
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Maxillofacial Diagnostic and Surgical Science, Graduate School of Dental Science, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiura
keywords: KLF4; SOX2; brachyury; lymph nodes; metastasis; squamous cell carcinoma