人原发性肝细胞癌中总基因组DNA甲基化变化的研究

Change of total genomic DNA methylation level in human hepatocellular carcinoma

目的：研究原发性肝细胞癌组织中总基因组DNA甲基化水平及其与病理学及生物学行为的关系。方法：以甲基化酶温育3H-腺苷甲硫氨酸掺入、液闪计数法分析33例中晚期肝癌手术标本的癌灶和癌旁组织细胞内总基因组DNA甲基化水乎，并以10例正常肝组织作对照比较。结果：肝癌灶内的DNA甲基化水平显著低于癌旁组织（P＜0．05）和正常对照肝组织（P＜0．01），其甲基化水平降低程度与肿瘤的大体形态（多发性或单灶性．结节型或区块型）有关，而与组织学改变（Edmondson分级）、门脉癌栓有否及血清AFP水平无明显关系。结论：人原发性肝细胞癌组织中DNA的甲基化水平有显著降低，值得进一步研究肝细胞癌组织个别癌基因片段甲基化及mRNA表达状况。

Objective: To examine the extent of total genomic DNA methylation in hepatocellular carcinoma and the relationship between the DNA hypomethylation. and histopatho-logic characteristics. Methods: Two groups of subjects were studied: 33 patients with hepatocellular carcinomas (HCC) and 10 healthy subjects as control. Total genomic DNA methylation wasevaluated in carcinomatous and paired-matched paracarcinomatous tissue of patients with HCC,compared with a group of control subjects, by incubating DNA with3H-S-adenosylmethionine inthe presence of methylase. The clinicopathological parameters were also analyzed. Results: DNA from carcinomatous lesions was more hypomethylated as compared with paired-matched paracarcinomatous lesions(P＜0.05). Significant difference was also observed when comparing the degree of DNA methylation of malignant tumors with that of control subjects (P＜0.01). DNA hypomethylation had a strong correlation with tumor number and size, but had no statistically significant correlation with the grade of histological differentiation and other clinicopathological parameters, including hepatitis virus infection, and the serum titers of alpha-fetoprotein.Conclusions: Our study demonstrates that DNA hypomethylation is present at the moderate and moderately advanced stages of liver carcinoma.