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目的通过分析宫颈上皮内瘤变(CIN)和宫颈癌组织中 p16、CDH1、RASSF1A和TIMP3基因 DNA 甲基化的变化情况,探讨其在宫颈癌发生中的意义。方法用甲基化特异性聚合酶链反应技术(MSP)对 CIN Ⅰ组(40份)、CIN Ⅱ～Ⅲ组(40份)、宫颈癌组(40份)病变组织中 p16、CDH1、RASSF1A 和 TIMP3基因 DNA 甲基化程度进行检测。另取正常宫颈组织20份作为对照组。结果 (1)对照组中 p16、CDH1、RASSF1A 和 TIMP3基因的 DNA 甲基化阳性率均为0。(2)p16和CDH1基因的 DNA 甲基化阳性率,CINⅡ～Ⅲ组(分别为22%、35%)明显高于 CIN Ⅰ组(分别为2%、5%,P<0.05);RASSF1A 和 TIMP3基因的 DNA 甲基化阳性率,CINⅡ～Ⅲ组(分别为12%、15%)虽高于 CIN Ⅰ组(均为2%),但差异无统计学意义(P>0.05)。(3)宫颈癌组 p16(40%)、CDH1(58%)、RASSF1A(20%)和 TIMP3(35%)基因的 DNA 甲基化阳性率虽均高于CINⅡ～Ⅲ组,但差异无统计学意义(P>0.05)。(4)宫颈癌组 p16、CDH1、RASSF1A 和 TIMP3基因的 DNA 甲基化阳性率均高于CIN Ⅰ组,差异有统计学意义(P<0.05)。(5)上述基因的 DNA 甲基化的总阳性率(即任何一个基因出现甲基化即为阳性),宫颈癌组(90%)明显高于 CINⅡ～Ⅲ组(55%,P<0.05),且此两组均明显高于 CIN Ⅰ组(8%,P<0.05)。结论随着从宫颈不典型增生向浸润癌的进展,p16、CDH1、RASSF1A和 TIMP3基因的 DNA 甲基化阳性率明显升高,提示抑癌基因的 DNA 甲基化在宫颈癌发生、发展中起着一定作用,可能成为判断宫颈癌发生、发展的重要指标。
Objective To investigate the changes of DNA methylation of p16, CDH1, RASSF1A and TIMP3 in cervical intraepithelial neoplasia (CIN) and cervical cancer and to explore its significance in cervical carcinogenesis. Methods The expressions of p16, CDH1, RASSF1A and C16 in CD8 + T cells of CIN Ⅰ group (40 cases), CIN Ⅱ ~ Ⅲ group (40 cases) and cervical cancer group (40 cases) were determined by methylation specific polymerase chain reaction TIMP3 gene DNA methylation levels were detected. Another 20 cases of normal cervical tissue as a control group. Results (1) The positive rates of DNA methylation of p16, CDH1, RASSF1A and TIMP3 in the control group were all 0. (2) The positive rate of DNA methylation of p16 and CDH1 was significantly higher in CINⅡ-Ⅲ group (22%, 35%, respectively) than that in CINⅠ group (2%, 5%, P < The positive rate of DNA methylation of TIMP3 gene was higher in CINⅡ-Ⅲ group (12% and 15%, respectively) than in CINⅠ group (both 2%), but the difference was not statistically significant (P> 0.05). (3) The positive rates of DNA methylation of p16 (40%), CDH1 (58%), RASSF1A (20%) and TIMP3 (35%) in cervical cancer group were higher than those in CINⅡ-Ⅲ group Significance (P> 0.05). (4) The positive rates of DNA methylation of p16, CDH1, RASSF1A and TIMP3 in cervical cancer group were significantly higher than those in CIN Ⅰ group (P <0.05). (5) The positive rate of DNA methylation (ie, methylation of any one gene was positive) in cervical cancer group (90%) was significantly higher than that of CIN Ⅱ ~ Ⅲ group (55%, P <0.05) , And both groups were significantly higher than CIN Ⅰ group (8%, P <0.05). Conclusion With the progression from cervical atypical hyperplasia to invasive carcinoma, the positive rate of DNA methylation of p16, CDH1, RASSF1A and TIMP3 genes is significantly increased, suggesting that DNA methylation of tumor suppressor genes plays an important role in the occurrence and development of cervical cancer A certain role, may become an important indicator of cervical cancer occurrence and development.