肝细胞癌患者癌组织中RASSF1A和WIF-1基因甲基化的临床意义

山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (5): 89-93.

肝细胞癌患者癌组织中RASSF1A和WIF-1基因甲基化的临床意义

范海燕，张慧景，郭占军，李胜棉

河北医科大学第四医院消化内科，石家庄 050011

收稿日期:2013-03-05 出版日期:2013-05-10 发布日期:2013-05-10
通讯作者: 李胜棉， E-mail: lishengmian@yahoo.com.cn

Prognostic significance of RASSF1A and WIF-1 methylation in the cancer tissues of patients with HCC

FAN Hai-yan， ZHANG Hui-jing， GUO Zhan-jun， LI Sheng-mian

Department of Gastroenterology， the Fourth Hospital of Hebei Medical University， Shijiazhuang 050011， China

Received:2013-03-05 Online:2013-05-10 Published:2013-05-10

摘要/Abstract

摘要：

目的观察肝细胞癌患者癌组织中RASSF1A基因甲基化状态的临床意义，阐明WIF-1基因甲基化在肝细胞癌发生发展中的作用。方法 97例肝细胞癌患者手术切除癌组织蜡块标本为肝细胞癌组，随机留取26例手术切除肝细胞癌旁肝硬化组织蜡块标本为肝硬化组。两组标本经蜡块组织DNA提取、亚硫酸盐甲基化修饰，并采用甲基化特异性PCR法对抑癌基因RASSF1A和WIF-1进行目的片段的扩增，扩增产物通过电泳凝胶成像系统进行甲基化结果分析判定；根据患者术前实验室检测是否感染HBsAg，将肝细胞癌组细分为HBsAg阳性组及HBsAg阴性组，分析抑癌基因RASSF1A和WIF-1甲基化的意义。结果 RASSF1A基因甲基化率肝细胞癌组(67.01%)高于肝硬化组(42.31%)，差异有统计学意义(P=0.021)；WIF-1基因甲基化率肝细胞癌组(46.39%)高于肝硬化组(7.69%)，差异有统计学意义(P<0.05)；肝细胞癌组中抑癌基因RASSF1A和WIF-1基因甲基化表达均阳性为35.05%，肝硬化组为7.69%，差异有统计学意义(P=0.006)。HBsAg阳性肝细胞癌组RASSF1A基因的甲基化阳性率(72.84%)高于HBsAg阴性组(23.08%)，差异有统计学意义(P=0.001)；WIF-1基因在HBsAg阳性(44.44%)和阴性肝细胞癌组(53.84%)差异无统计学意义(P=0.528)。肝细胞癌患者RASSF1A和WIF-1基因的甲基化状态与生存率比较差异无统计学意义(P=0.735，P=0.229)。结论肝细胞癌患者癌组织较肝硬化组织RASSF1A，WIF-1基因甲基化率高，提示抑癌基因RASSF1A和WIF-1的甲基化在肝细胞癌的发生中起到一定作用。

关键词: 肝细胞癌；抑癌基因；RASSF1A；WIF-1；甲基化

Abstract:

Objective To study the clinical significance of RASSF1A methylation in the cancer tissues of patients with HCC and explore the effect of WIF-1 methylation in the genesis and development of HCC. Methods 97 cancer tissue samples of patients with hepatocellular carcinoma (HCC group) and 26 samples of adjacent liver cirrhosis (cirrhosis group) were studied. DNA extraction and sulfites methylation modification was carried out in the two groups of samples. Methylation specific PCR of these two tumor suppressor genes was run, and the methylation status was assessed subsequently. Depending on whether the patients were infected by HbsAg before operation or not, the hepatocellular carcinoma group was subdivided into the HBsAg-positive group and the HBsAg-negative group. The significance of the tumor suppressor genes RASSF1A and WIF-1 methylation was analysed. Results The ratio of the two suppressor genes (RASSF1A and WIF-1) methylation in the HCC group(67.01% and 46.39%)was higher than that of the cirrhosis group(42.31% and 7.69%)The difference was statistically significant(P<0.05 ). There was statistically significant difference in the two genes positive methylation expression between the two groups(35.05% and 7.69%， P=0.006). Significant difference for the suppressor gene RASSF1A in the HBsAg positive and negative groups was confirmed(72.84% and 23.08%， P=0.001), but not for WIF-1 gene(44.44% and 53.84%， P=0.528). No significant difference between the tumor suppressor genes RASSF1A and WIF-1 methylation in the patients with HCC and survival rate could be found(P=0.735， P=0.229). Conclusion The methylation ratio of the two suppressor genes (RASSF1A, WIF-1) in the cancerous tissues is higher than that in the adjacent non-cancerous cirrhosis tissues of HCC patients, which suggests that the methylation of the suppressor genes RASSF1A and WIF-1 may play an important role in HCC carcinogenesis.

Key words: Hepatocellular carcinoma； Supressor gene； RASSF1A； WIF-1； Methylation

中图分类号:

R735.7

范海燕，张慧景，郭占军，李胜棉. 肝细胞癌患者癌组织中RASSF1A和WIF-1基因甲基化的临床意义[J]. 山东大学学报(医学版), 2013, 51(5): 89-93.

FAN Hai-yan， ZHANG Hui-jing， GUO Zhan-jun， LI Sheng-mian. Prognostic significance of RASSF1A and WIF-1 methylation in the cancer tissues of patients with HCC[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(5): 89-93.

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