文章：

非肝硬化性肝细胞癌中DNA甲基化标志物的高甲基化

Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma

原文发布日期：28 September 2023

DOI: 10.3390/cancers15194784

类型: Article

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英文摘要：

Aberrant DNA methylation changes have been reported to be associated with carcinogenesis in cirrhotic HCC, but DNA methylation patterns for these non-cirrhotic HCC cases were not examined. Therefore, we sought to investigate DNA methylation changes on non-cirrhotic HCC using reported promising DNA methylation markers (DMMs), including HOXA1, CLEC11A, AK055957, and TSPYL5, on 146 liver tissues using quantitative methylation-specific PCR and methylated DNA sequencing. We observed a high frequency of aberrant methylation changes in the four DMMs through both techniques in non-cirrhotic HCC compared to cirrhosis, hepatitis, and benign lesions (p< 0.05), suggesting that hypermethylation of these DMMs is specific to non-cirrhotic HCC development. Also, the combination of the four DMMs exhibited 78% sensitivity at 80% specificity with an AUC of 0.85 in discriminating non-cirrhotic HCC from hepatitis and benign lesions. In addition, HOXA1 showed a higher aberrant methylation percentage in non-cirrhotic HCC compared to cirrhotic HCC (43.3% versus 13.3%,p= 0.039), which was confirmed using multivariate linear regression (p< 0.05). In summary, we identified aberrant hypermethylation changes in HOXA1, CLEC11A, AK055957, and TSPYL5 in non-cirrhotic HCC tissues compared to cirrhosis, hepatitis, and benign lesions, providing information that could be used as potentially detectable biomarkers for these unusual HCC cases in clinical practice.

摘要翻译： 

已有研究报道异常DNA甲基化改变与肝硬化性肝细胞癌（HCC）的癌变过程相关，但非肝硬化性HCC病例的DNA甲基化模式尚未得到系统研究。为此，我们采用定量甲基化特异性PCR和甲基化DNA测序技术，对146例肝组织中包括HOXA1、CLEC11A、AK055957和TSPYL5在内的潜在DNA甲基化标志物进行检测，以探究非肝硬化性HCC的DNA甲基化改变。通过两种技术均观察到，与肝硬化、肝炎及良性病变相比，非肝硬化性HCC中四种标志物呈现高频异常甲基化改变（p<0.05），提示这些标志物的高甲基化是非肝硬化性HCC发展的特异性表现。四种标志物联合检测在区分非肝硬化性HCC与肝炎及良性病变时，以80%特异性达到78%灵敏度，曲线下面积（AUC）为0.85。此外，HOXA1在非肝硬化性HCC中的异常甲基化比例显著高于肝硬化性HCC（43.3%对比13.3%，p=0.039），该结果经多元线性回归验证具有统计学意义（p<0.05）。综上所述，本研究首次在非肝硬化性HCC组织中鉴定出HOXA1、CLEC11A、AK055957和TSPYL5的特异性异常高甲基化改变，为临床实践中检测这类特殊类型HCC提供了潜在的生物标志物信息。

原文链接：

Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma