DNA 甲基转移酶作为 HCV 相关肝细胞癌的潜在生物标志物。
DNA Methyltransferases as Potential Biomarkers for HCV Related Hepatocellular Carcinoma.
机构信息
Department of Clinical and Chemical Pathology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt.
Department of Clinical pathology, National Cancer Institute, Cairo University, Cairo, Egypt.
出版信息
Asian Pac J Cancer Prev. 2020 Nov 1;21(11):3357-3363. doi: 10.31557/APJCP.2020.21.11.3357.
BACKGROUND
Hepatocellular carcinoma (HCC) is a major health concern in many countries including Egypt. The alteration in DNA methylation that was observed in HCC patients suggests a possible role of DNA methyltransferases (DNMTs) in the disease pathogenesis in addition to potential role as a disease biomarker.
AIM
To study the change in DNMTs expression in chronic HCV infected patients as potential non- invasive biomarker for diagnosis of hepatocellular carcinoma.
METHODS
26 patients with HCC, 45 patients with liver cirrhosis, 20 chronic HCV patients and 20 apparently healthy individuals as a control group were enrolled in this study. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed for all study participants.
RESULTS
A significant difference in DNMTs expression was observed among the studied groups. Receiver operating characteristics (ROC) curve analysis revealed that with a cutoff value of 3.16 for DNMT 3A expression, sensitivity and specificity were 80.8 and 95.6% respectively and area under curve (AUC) was 0.958, p < 0.001 for discriminating hepatocellular carcinoma among post hepatitis C cirrhotic patients. Besides DNMT 3B relative expression cutoff value of 3.10 showed 84.6% sensitivity and 77.8% specificity and AUC was 0.888, p < 0.001. On the other hand, cutoff value 0.65 for DNMT1 relative expression showed 92.3% sensitivity and 44.4% specificity and AUC was 0.72, p= 0.002. DNMT1, DNMT 3A and DNMT 3B have significant positive correlation with the level of AFP (p-value = 0.003, 0.004 and 0.008 respectively). The relative expression of DNMT3B was significantly correlated to focal lesion size (p-value = 0.015). High DNMTs expression was significantly associated with the presence of multiple focal lesions but not with the Child Pugh grade (p> 0.05).
CONCLUSION
The mRNA levels of DNMTs could be a potential biomarker for early detection of HCC development.
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背景
肝癌（HCC）是包括埃及在内的许多国家的主要健康问题。在 HCC 患者中观察到的 DNA 甲基化改变表明，DNA 甲基转移酶（DNMTs）除了作为疾病生物标志物外，可能在疾病发病机制中发挥作用。
目的：研究慢性 HCV 感染患者中 DNMTs 表达的变化，作为诊断肝细胞癌的潜在非侵入性生物标志物。
方法：本研究纳入 26 例 HCC 患者、45 例肝硬化患者、20 例慢性 HCV 患者和 20 例健康个体作为对照组。对所有研究对象进行实时定量逆转录 PCR（qRT-PCR）。
结果：研究组间 DNMTs 表达存在显著差异。接受者操作特征（ROC）曲线分析显示，以 DNMT3A 表达的截断值 3.16 为界，对慢性丙型肝炎后肝硬化患者中 HCC 的诊断具有 80.8%的敏感性和 95.6%的特异性，曲线下面积（AUC）为 0.958，p<0.001。此外，DNMT3B 相对表达的截断值 3.10 显示出 84.6%的敏感性和 77.8%的特异性，AUC 为 0.888，p<0.001。另一方面，DNMT1 相对表达的截断值 0.65 显示出 92.3%的敏感性和 44.4%的特异性，AUC 为 0.72，p=0.002。DNMT1、DNMT3A 和 DNMT3B 与 AFP 水平呈显著正相关（p 值分别为 0.003、0.004 和 0.008）。DNMT3B 的相对表达与局灶性病变大小显著相关（p 值为 0.015）。高 DNMTs 表达与多发性局灶性病变的存在显著相关，但与 Child Pugh 分级无关（p>0.05）。
结论：DNMTs 的 mRNA 水平可能是早期检测 HCC 发展的潜在生物标志物。
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