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肿瘤抑制基因的甲基化与丙型肝炎病毒相关肝硬化及肝细胞癌

Methylation of tumour suppressor genes and in HCV-related liver cirrhosis and hepatocellular carcinoma.

作者信息

El-Bendary Mahmoud, Nour Dina, Arafa Mona, Neamatallah Mustafa

机构信息

Tropical Medicine and Hepatology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Mansoura Fever Hospital, Ministry of Health, Mansoura, Egypt.

出版信息

Br J Biomed Sci. 2020 Jan;77(1):35-40. doi: 10.1080/09674845.2019.1694123. Epub 2019 Dec 2.

DOI:10.1080/09674845.2019.1694123
PMID:31790342
Abstract

: HCV infection is related to aberrant methylation of several genes. and are tumour suppressor genes that may be inactivated by hypermethylation in many tumours including hepatocellular carcinoma (HCC). We hypothesized that methylation is a diagnostic biomarker for HCC in patients with HCV-related liver cirrhosis.: We recruited 207 cases of HCV-related liver cirrhosis, 193 HCC patients and 53 healthy controls. Methylation-specific polymerase chain reaction for detection of circulating hypermethylated and . Alpha fetoprotein (AFP) was measured by commercial immunoassay.: Significant hypermethylation of the three genes was found in the HCC group compared to both cirrhosis and healthy groups ( < 0.001), whereas no significant difference in hypermethylation was found between cirrhosis and healthy groups ( = 0.17, 0.50 and 0.14, respectively). No significant links were found between hypermethylated and and stages of Barcelona Clinic of Liver Cancer score (0.21, 0.63 and 0.98, respectively). No significant associations were found between AFP value and hypermethylated genes in cirrhosis and HCC groups ( = 0.82) except with in HCC ( = 0.02). In multiple regression analysis, and were predictors of HCC within cirrhosis cases, but only was an independent risk factor for prediction of HCC in cases with low AFP ( = 0.01).: The presence of hypermethylated serum and is linked to HCC in patients with HCV-related cirrhosis. Only is an independent risk factor for prediction of HCC with low AFP. These findings may be of diagnostic value.

摘要

丙型肝炎病毒(HCV)感染与多个基因的异常甲基化有关。[基因名称1]和[基因名称2]是肿瘤抑制基因,在包括肝细胞癌(HCC)在内的许多肿瘤中可能因高甲基化而失活。我们推测甲基化是HCV相关肝硬化患者HCC的诊断生物标志物。

我们招募了207例HCV相关肝硬化患者、193例HCC患者和53名健康对照者。采用甲基化特异性聚合酶链反应检测循环中的高甲基化[基因名称1]和[基因名称2]。通过商业免疫测定法检测甲胎蛋白(AFP)。

与肝硬化组和健康组相比,HCC组中这三个基因均有显著的高甲基化(P<0.001),而肝硬化组和健康组之间在高甲基化方面未发现显著差异(P分别为0.17、0.50和0.14)。高甲基化的[基因名称1]和[基因名称2]与巴塞罗那肝癌临床分期之间未发现显著关联(P分别为0.21、0.63和0.98)。除了HCC组中[基因名称3]与AFP值有显著关联(P=0.02)外,肝硬化组和HCC组中AFP值与高甲基化基因之间未发现显著关联(P=0.82)。在多元回归分析中,[基因名称1]和[基因名称2]是肝硬化病例中HCC的预测因子,但只有[基因名称4]是低AFP病例中预测HCC的独立危险因素(P=0.01)。

血清中高甲基化的[基因名称1]和[基因名称2]与HCV相关肝硬化患者的HCC有关。只有[基因名称4]是低AFP情况下预测HCC的独立危险因素。这些发现可能具有诊断价值。

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