卵巢肿瘤组织和血清中RASSF1A基因甲基化检测及临床意义的研究

Detection of aberrant methylation of RASSF1A gene in the tissue and the serum from ovarian tumor patients and its clinical significance

目的:检测卵巢肿瘤组织和血清中RASSF1A基因启动子区异常甲基化,探讨卵巢肿瘤组织和血清中RASSF1A基因甲基化与卵巢癌的关系。方法:收集新鲜的卵巢肿瘤组织及其对应的血清标本65例,10名健康志愿者血清标本。采用半巢式甲基化特异性PCR技术分别检测肿瘤组织DNA和血清游离DNA中RASSF1A基因启动子异常甲基化情况。结果:卵巢癌患者血清和癌组织中,RASSF1A基因甲基化的检出率分别为20.0%和31.4%。卵巢良性肿瘤组织和血清以及健康志愿者血清中,均未发生RASSF1A基因异常甲基化。肿瘤组织中,RASSF1A基因的甲基化状况与血清中出现RASSF1A基因甲基化关系密切,P<0.01;卵巢癌患者血清和癌组织中,RASSF1A基因的甲基化异常改变与肿瘤的临床分期、细胞分化程度以及组织学类型无明显相关性,P>0.05;与淋巴结转移密切相关,P<0.05。结论:分析血清DNA的RASSF1A基因异常甲基化有可能成为辅助卵巢癌诊断的有效方法之一。

OBJECTIVE.. To detect hypermethylation of RASSF1A gene in the tissue and the serum from ovarian tumor patients, and to explore its correlation with ovarian cancer. METHODS： Sixty five tissue samples and their corresponding serum samples from ovarian tumor patients, 10 serum sampales from healthy volunteers were collected for hypermethylation measurement by semi-nested methylation-specific PCR （MSP）. RESULTS： Hypermethylation of RASSF1A was present in 20.0%（7/35） of the cancer serum samples and 31.4% （11/35） of the cancer tissues. None of benign ovarian disease tissues and serums was methylated. Hypermethylation of RASSF1A was not found in serum samples from healthy volunteers. There was a statistical association between hypermethylation of RASSF1A in serums and that of RASSF1A in tumor tissues （P〈0.01）. Hypermethylation of the RASSF1A in serums and the corresponding cancer tissues was not significantly correlated with the clinical stages, histologic cell types, degrees of cell differentiation of the tumor （P〉0.05）, but it was strongly correlated with lymph node metastasis （P〈 0.05）. CONCLUSION： The result indicated that hypermethylation of the RASSF1A may be a useful marker in the auxiliary diagnosis of ovarian cancer.