首页|Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
  • 维普
Background:Glycine dehydrogenase(GLDC)plays an important role in the initiation and proliferation of several human cancers.In this study,we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC).Methods:We enrolled 197 patients,111 with HBV-HCC,51 with chronic hepatitis B(CHB),and 35 healthy controls(HCs).The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs)was identified by methylation specific polymerase chain reaction(MSP).The mRNA expression was examined using real-time quantitative polymerase chain reaction(qPCR).Results:The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0％)compared to that in CHB patients(68.6％)and HCs(74.3％)(P＜0.001).The methylated group had lower alanine aminotransferase level(P=0.035)and lower rates of tumor node metastasis(TNM)Ⅲ/Ⅳ(P=0.043)and T3/T4(P=0.026).TNM stage was identified to be an independent factor for GLDC pro-moter methylation.GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients(P=0.022 and P＜0.001,respectively).GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters(P=0.003).The diagnostic accuracy of alpha-fetoprotein(AFP)combined with GLDC promoter methy-lation for HBV-HCC was improved compared with that of AFP alone(AUC:0.782 vs.0.630,P＜0.001).In addition,GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients(P=0.038).Conclusions:The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs.The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

Hepatocellular carcinomaGlycine dehydrogenaseDNA methylationPeripheral blood mononuclear cells

Li-Li Miao、Jing-Wen Wang、Hui-Hui Liu、Shuai Gao、Yu-Chen Fan、Kai Wang

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Department of Hepatology,Qilu Hospital of Shandong University,Jinan 250012,China

Experimental Center,Shandong University of Traditional Chinese Medicine,Jinan 250355,China

Institute of Hepatology,Shandong University,Jinan 250012,China

Key Project of the Chinese Ministry of Science and TechnologyNational Key Research and Development Program of China

2017ZX1020220222021YFC2301801

2024

10.1016/j.hbpd.2023.02.011

国际肝胆胰疾病杂志(英文版)
浙江省医学学术交流管理中心,浙江大学医学院附属第一医院,浙江大学出版社有限责任公司

国际肝胆胰疾病杂志(英文版)

影响因子：0.668
ISSN：1499-3872
年,卷(期)：2024.23(1)
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