研究 APC、P14 和 E-钙黏蛋白基因异常甲基化在 HCV 相关肝癌发生中的频率。

Studying the frequency of aberrant DNA methylation of APC, P14, and E-cadherin genes in HCV-related hepatocarcinogenesis.

机构信息

Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Department of Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.

出版信息

Cancer Biomark. 2018;22(3):503-509. doi: 10.3233/CBM-171156.

DOI:10.3233/CBM-171156

PMID:29865038

Abstract

BACKGROUND

Data about the molecular pathogenesis of hepatitis C-related hepatocellular carcinoma (HCC) are still challenging.

OBJECTIVES

Therefore, we tried to investigate the epigenetic study of three nominated genes (APC, P14, and E-cadherin) in the pathogenesis of HCV-related HCC in Egyptian.

METHODS

Between March 2016 and March 2017, the DNA methylation, and quantification using (epigenetic ELISA kit) for E-cadherin, APC, and P14 genes were studied in three groups of patients: HCV related liver cirrhosis without HCC group (LC-group; n= 20), HCC on top of HCV-related cirrhosis (HCC-group; n= 20), and a third apparently healthy control group (control-group; n= 10).

RESULTS

E-cad methylation showed non-significant differences between groups. P14 methylation was occurred only in HCC-group (45%). APC methylation was the highest in HCC group (70%). Methylation level was high in HCC group in comparison to both LC and control groups (P< 0.001). DNA methylation at a cutoff point > 2.9 ng/ml predicts HCC in LC-group with 90% sensitivity and 80% specificity and at level > 2.3 ng/ml had 95% sensitivity and 90% specificity in control-group. The pooled sensitivity, specificity, positive and negative predictive values and accuracy were 90%, 60%, 69.2, 85.7 and 75% respectively.

CONCLUSION

Aberrant DNA methylation of multiple genes is associated with disease progression in HCV related cirrhosis. Moreover, early detection of promotor methylation of these may sever as good biomarker for early detection and therapeutic targets in high risk patients.

摘要

背景

有关丙型肝炎相关肝细胞癌（HCC）的分子发病机制的数据仍然具有挑战性。

目的

因此，我们试图在埃及研究三个提名基因（APC、P14 和 E-钙黏蛋白）在 HCV 相关 HCC 发病机制中的表观遗传学研究。

方法

2016 年 3 月至 2017 年 3 月，我们研究了三组患者的 DNA 甲基化和使用（表观遗传 ELISA 试剂盒）对 E-钙黏蛋白、APC 和 P14 基因的定量：HCV 相关肝硬化无 HCC 组（LC 组；n=20）、HCV 相关肝硬化上的 HCC 组（HCC 组；n=20）和第三组明显健康对照组（对照组；n=10）。

结果

E-钙黏蛋白的甲基化在各组之间无显著差异。P14 甲基化仅发生在 HCC 组（45%）。APC 甲基化在 HCC 组中最高（70%）。与 LC 组和对照组相比，HCC 组的甲基化水平更高（P<0.001）。在 LC 组中，甲基化水平>2.9ng/ml 预测 HCC 的灵敏度为 90%，特异性为 80%，在对照组中，甲基化水平>2.3ng/ml 预测 HCC 的灵敏度为 95%，特异性为 90%。敏感性、特异性、阳性预测值、阴性预测值和准确性的合并值分别为 90%、60%、69.2%、85.7%和 75%。