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Metallophosphoesterase 1, a novel candidate gene in hepatocellular carcinoma malignancy and recurrence

机译：金属膦酯酶1，肝细胞癌恶性肿瘤的新候选基因

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摘要

Background There is an unmet need to identify novel mechanism-based prognostic genes associated with hepatocellular carcinoma (HCC) recurrence that can predict patient outcomes and provide therapeutic targets. This study aims to identify potential novel driver genes and mutations in HCC. Methods Single nucleotide variations (SNVs) contributing to HCC recurrence were identified using whole-exome sequencing of 5 DNA samples extracted from a single HCC patient with HBV-induced cirrhosis. SNVs were verified in primary HCC (n = 87), recurrent HCC (n = 34), and benign liver disease with cirrhosis tissues (n = 43). A candidate gene was identified, and its association and function in HCC development and recurrence were examined. Results 177 SNVs were identified and 70 SNVs were verified. AMPPE1missense mutation on chr18_11897016 was the most frequent mutation (16.5%) in primary and recurrent HCC tissues, occurring with a higher frequency in recurrent HCC than primary HCC or benign liver tumor tissues. TheMPPE1mutation was significantly associated with HCC recurrence (P= .003), TNM stage (P= .002), and Child-Pugh classification (P= .039), and was an independent risk factor for HCC recurrence (HR = 1.969; 95%CI = 1.043-3.714,P= .037). Analysis of publically available data deposited in the GEO and TCGA showed MPPE1 expression levels were significantly increased in HCC tumor samples compared to adjacent nontumor tissues. The knockdown of MPPE1 in HCC cell lines significantly inhibited cell proliferation, migration and invasion, induced cell cycle arrest and apoptosisin vitro, and inhibited xenograft tumor growth in nude micein vivo(P< .05). Conclusions MPPE1is a novel gene associated with HCC malignancy and recurrence.
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  • 来源
    《Cancer biology & therapy》 |2020年第12期|共9页
  • 作者

    Chen Xinguo; Xu Jing; Wang Peixiao; Shang Lei; Guo Jing; Huang Lihong; Jiang Yide A.; Chen Jinhong; Chen Huijuan; Shang Yukui; Zhang Qing;

  • 作者单位

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Inst Liver Surg Beijing Peoples R China;

    Southern Univ Sci &

    Technol Hosp Med Res Ctr Shenzhen Peoples R China;

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Inst Liver Surg Beijing Peoples R China;

    Fourth Mil Med Univ Fac Prevent Med Dept Hlth Stat Xian Peoples R China;

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Med Dept Beijing Peoples R China;

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Med Dept Beijing Peoples R China;

    Genzyme Inst Sanofi Genzyme R&

    D Ctr Framingham MA USA;

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Med Dept Beijing Peoples R China;

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Inst Liver Surg Beijing Peoples R China;

    Fourth Mil Med Univ Natl Translat Sci Ctr Mol Med Xian Peoples R China;

    Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Inst Liver Surg Beijing Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

    Metallophosphoesterase 1; hepatocellular carcinoma; tumor recurrence; whole-exome sequencing;

    机译：金属膦酯酶1;肝细胞癌;肿瘤复发;全外测序;

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