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

Yoshihama,Rumi; Yamaguchi,Koujiro; Imajyo,Ikumi; Mine,Mariko; Hiyake,Naomi; Akimoto,Naonari; Kobayashi,Yosuke; Chigita,Satomi; Kumamaru,Wataru; Kiyoshima,Tamotsu; Mori,Yoshihide; Sugiura,Tsuyoshi

doi:10.3892/ol.2015.4047

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

Authors:
- Rumi Yoshihama
- Koujiro Yamaguchi
- Ikumi Imajyo
- Mariko Mine
- Naomi Hiyake
- Naonari Akimoto
- Yosuke Kobayashi
- Satomi Chigita
- Wataru Kumamaru
- Tamotsu Kiyoshima
- Yoshihide Mori
- Tsuyoshi Sugiura
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Affiliations: Department of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812‑8582, Japan, Department of Maxillofacial Diagnostic and Surgical Science, Graduate School of Dental Science, Kagoshima University, Kagoshima 890‑8544, Japan, Department of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka 812‑8582, Japan
Published online on: December 22, 2015 https://doi.org/10.3892/ol.2015.4047
Pages: 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 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.

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