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Research Article

Methylation of TFPI-2 is an early event of esophageal carcinogenesis

    Yan Jia

    Department of Gastroenterology & Hepatology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China

    Medical College of NanKai University, 94 Weijin Road, Tianjin 300071, China

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    ,
    Yunsheng Yang

    Department of Gastroenterology & Hepatology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China

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    ,
    Malcolm V Brock

    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting–Blaustein Cancer Research Building, Room 543, 1650 Orleans Street, Baltimore, MD 21231, USA

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    ,
    Baoping Cao

    Department of Gastroenterology & Hepatology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China

    Medical College of NanKai University, 94 Weijin Road, Tianjin 300071, China

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    ,
    Qimin Zhan

    State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China

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    ,
    Yazhuo Li

    Department of Pathology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China

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    ,
    Yuanzi Yu

    Department of Gastroenterology & Hepatology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China

    Medical College of NanKai University, 94 Weijin Road, Tianjin 300071, China

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    ,
    James G Herman‡

    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting–Blaustein Cancer Research Building, Room 543, 1650 Orleans Street, Baltimore, MD 21231, USA

    ‡Authors contributed equally.

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    &
    Mingzhou Guo‡

    * Author for correspondence

    Department of Gastroenterology & Hepatology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China.

    ‡Authors contributed equally.

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    Email the corresponding author at mzguo1@gmail.com

    Published Online:27 Mar 2012https://doi.org/10.2217/epi.12.11

    Abstract

    Aims: To explore the epigenetic changes and the function of TFPI-2 in esophageal cancer. Materials & methods: Nine esophageal cancer cell lines, nine normal esophageal mucosa, 60 esophageal dysplasia and 106 advanced esophageal cancer samples were included in this study. TFPI-2 methylation was examined by methylation-specific PCR. TFPI-2 expression was evaluated by immunohistochemistry in tissue samples. The effect of TFPI-2 on proliferation, apoptosis, invasion and migration was analyzed by colony formation assay, western blot assay, transwell assay and flow cytometric analysis. Results: TFPI-2 expression was regulated by promoter region hypermethylation in human esophageal cancer cell lines, and TFPI-2 expression is inversely correlated with methylation in primary cancer. Methylation was found in 28.2, 33.3 and 33.3% of grade 1, 2 and 3 esophageal dysplasia, and 67% of primary esophageal cancer, but no methylation was found in normal mucosa. Methylation is significantly related to tumor differentiation. Inhibition of invasion, migration, colony formation and proliferation, and induction of apoptosis occurred with the restoration of TFPI-2 expression in the KYSE70 cell line. Conclusion:TFPI-2 is frequently methylated in esophageal cancer with a progression tendency. TFPI-2 is a potential tumor suppressor in esophageal cancer.

    Papers of special note have been highlighted as: ▪ of interest

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