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SOX9 expression and its methylation status in gastric cancer

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Abstract

SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family and is required for the development and differentiation of multiple cell lineages. To clarify the significance of SOX9 in gastric carcinoma (GC), immunohistochemical expression of SOX9 and the CpG island methylation status of SOX9 were evaluated and compared with clinicopathological factors including overall survival. SOX9 expression was immunohistochemically evaluated in 382 GC tumors and the methylation status was examined in 121 GC tumors. SOX9 expression and its methylation status in six GC cell lines, their Epstein–Barr virus (EBV)-infected cell lines, and two EBV-associated GC cell lines was also examined. The SOX9 expression increased from non-neoplastic mucosa to early cancer. High expression of SOX9 was seen in 212 cases (56%). SOX9 expression was inversely related to advanced tumor stage, vessel infiltration, nodal metastasis, and EBV infection. Fifty-eight (48%) of 121 GC tumors had a methylated promoter in GC and the methylated status was related to low expression. The expression and methylation status were not related to prognosis. Three of six cell lines had increased methylation through EBV infection and decreased SOX9 expression. Upregulation of SOX9 is related to GC development. Downregulation by promoter methylation is related to GC progression and EBV infection. SOX9 is closely related to GC carcinogenesis and EBV-associated GC carcinogenesis.

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Acknowledgment

This study was supported by grants-in-aid for scientific research on priority areas (20249022, 20590337) and the Global COE Research Program “Comprehensive center of education and research for chemical biology of the diseases” from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflicts of interest

We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Minhua Sun, Hiroshi Uozaki, Rumi Hino, Akiko Kunita, Aya Shinozaki, Tetsuo Ushiku, Takashi Hibiya, Kimiko Takeshita, Maya Isogai & Masashi Fukayama

  2. Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

    Kenzo Takada

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  1. Minhua Sun
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  2. Hiroshi Uozaki
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Correspondence to Hiroshi Uozaki.

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Sun, M., Uozaki, H., Hino, R. et al. SOX9 expression and its methylation status in gastric cancer. Virchows Arch 460, 271–279 (2012). https://doi.org/10.1007/s00428-012-1201-7

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  • DOI: https://doi.org/10.1007/s00428-012-1201-7

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