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

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

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)1435-1446
ページ数12
ジャーナルOncology Letters
11
発行部数2
DOI
出版物ステータス出版済み - 2 2016

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Squamous Cell Carcinoma
Transcription Factors
Neoplasm Metastasis
Octamer Transcription Factors
Survival Rate
Lymph Nodes
Odds Ratio
Neoplastic Stem Cells
Oncogenes
Disease-Free Survival
Brachyury protein
Neoplasms
Stem Cells
Multivariate Analysis
Immunohistochemistry
Biopsy
Recurrence
Survival
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

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.

:: Oncology Letters, 巻 11, 番号 2, 02.2016, p. 1435-1446.

研究成果: ジャーナルへの寄稿記事

Yoshihama, Rumi ; Yamaguchi, Koujiro ; Imajyo, Ikumi ; Mine, Mariko ; Hiyake, Naomi ; Akimoto, Naonari ; Kobayashi, Yosuke ; Chigita, Satomi ; Kumamaru, Wataru ; Kiyoshima, Tamotsu ; Mori, Yoshihide ; Sugiura, Tsuyoshi. / Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma. :: Oncology Letters. 2016 ; 巻 11, 番号 2. pp. 1435-1446.
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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), Kr{\"u}ppel-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.",
author = "Rumi Yoshihama and Koujiro Yamaguchi and Ikumi Imajyo and Mariko Mine and Naomi Hiyake and Naonari Akimoto and Yosuke Kobayashi and Satomi Chigita and Wataru Kumamaru and Tamotsu Kiyoshima and Yoshihide Mori and Tsuyoshi Sugiura",
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T1 - Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

AU - Yoshihama, Rumi

AU - Yamaguchi, Koujiro

AU - Imajyo, Ikumi

AU - Mine, Mariko

AU - Hiyake, Naomi

AU - Akimoto, Naonari

AU - Kobayashi, Yosuke

AU - Chigita, Satomi

AU - Kumamaru, Wataru

AU - Kiyoshima, Tamotsu

AU - Mori, Yoshihide

AU - Sugiura, Tsuyoshi

PY - 2016/2

Y1 - 2016/2

N2 - 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.

AB - 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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