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

作　　者：Li-Li Miao Jing-Wen Wang Hui-Hui Liu Shuai Gao Yu-Chen Fan Kai Wang 

机构地区：[1]Department of Hepatology,Qilu Hospital of Shandong University,Jinan 250012,China [2]Experimental Center,Shandong University of Traditional Chinese Medicine,Jinan 250355,China [3]Institute of Hepatology,Shandong University,Jinan 250012,China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2024年第1期35-42,共8页国际肝胆胰疾病杂志（英文版）

基　　金：This study was supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022);National Key Research and Development Program of China(2021YFC2301801).

摘　　要：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(q PCR). 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 promoter 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 methylation 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.

关 键 词：Hepatocellular carcinoma Glycine dehydrogenase DNA methylation Peripheral blood mononuclear cells 

分 类 号：R735.7[医药卫生—肿瘤]