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

Chen，Xinguo1; Xu，Jing2,3; Wang，Peixiao1,4; Shang，Lei5; Guo，Jing6; Huang，Lihong6; Jiang，Yide A.7; Chen，Jinhong6; Chen，Huijuan1; Shang，Yukui3; Zhang，Qing1

2020

10.1080/15384047.2020.1824480

CANCER BIOLOGY & THERAPY   影响因子和分区

1538-4047

1555-8576

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. A MPPE1 missense 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. The MPPE1 mutation 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 apoptosis in vitro, and inhibited xenograft tumor growth in nude mice in vivo (P < .05). Conclusions: MPPE1 is a novel gene associated with HCC malignancy and recurrence.

hepatocellular carcinoma Metallophosphoesterase 1 tumor recurrence whole-exome sequencing

SCI

英语

其他

National Natural Science Foundation of China[81372595][31371376] ; Chinese State Key Projects for Basic Research and Development Program (973 Program)[2014-CBA02001]

Oncology

Oncology

WOS:000577724700001

TAYLOR & FRANCIS INC

CLINICAL MEDICINE

2-s2.0-85092611585

Scopus

1.Institute of Liver Surgery,Third Medical Centre of Chinese,PLA General Hospital,Beijing,China
2.Medical Research Center,Southern University of Science and Technology Hospital,Shenzhen,China
3.National Translational,Science Center for Molecular Medicine Department of Cell Biology,The Fourth Military Medical University,Xi’an,China
4.Department of Gastroenterology,Henan Children’s Hospital,Zhengzhou,China
5.Department of Health Statistics,Faculty of Preventive Medicine,Fourth Military Medical University,Xi’an,China
6.Medical Department,Third Medical Centre of Chinese,PLA General Hospital,Beijing,China
7.Institute of Sanofi Genzyme RD Center,Genzyme - a Sanofi Company,Framingham,United States

Chen，Xinguo,Xu，Jing,Wang，Peixiao,et al. Metallophosphoesterase 1, a novel candidate gene in hepatocellular carcinoma malignancy and recurrence[J]. CANCER BIOLOGY & THERAPY,2020,21(11):1005-1013.

Chen，Xinguo.,Xu，Jing.,Wang，Peixiao.,Shang，Lei.,Guo，Jing.,...&Zhang，Qing.(2020).Metallophosphoesterase 1, a novel candidate gene in hepatocellular carcinoma malignancy and recurrence.CANCER BIOLOGY & THERAPY,21(11),1005-1013.

Chen，Xinguo,et al."Metallophosphoesterase 1, a novel candidate gene in hepatocellular carcinoma malignancy and recurrence".CANCER BIOLOGY & THERAPY 21.11(2020):1005-1013.