抑癌基因XAF1和BNIP3表达及其异常甲基化与宫颈病变相关性研究

Correlation between expression and abnormal methylation of tumor suppressor genes XAFl and BNIP3 and cervicallesions

目的探讨抑癌基因XAF1和BNIP3表达及其异常甲基化与宫颈病变的关系。方法选择140例手术切除并经病理证实的标本,其中宫颈癌组48例,宫颈上皮内瘤样病变2~3级组织(CIN2-3组)32例,宫颈皮内瘤样病变1级组织(CIN1组)30例,正常宫颈组织(对照组)30例,采用甲基化特异性聚合酶链式反应(MSP)法及免疫组化(SP)法,检测上述各组中XAF1和BNIP3启动子区甲基化状态及蛋白表达水平。结果正常宫颈组、CIN1组、CIN2-3组、宫颈癌组XAF1基因启动子甲基化阳性率分别为3.3%、6.6%、37.5%、60.4%,正常宫颈组与CIN1组甲基化阳性率比较,差异无统计学意义(P>0.05);CIN1组与CIN2-3及宫颈癌组甲基化阳性率比较,差异均有统计学意义(P<0.05);正常宫颈组、CIN1组、CIN2-3组、宫颈癌组BNIP3基因甲基化阳性率分别为16.7%、20.0%、43.8%、68.8%,正常宫颈组与CIN1组甲基化阳性率比较,差异无统计学意义(P>0.05);CIN1组与CIN2-3及宫颈癌组甲基化阳性率比较,差异有统计学意义(P<0.05);正常宫颈组、CIN1组、CIN2-3组、宫颈癌组XAF1蛋白的阳性表达率分别为73.3%、76.7%、40.6%、10.4%,宫颈组与CIN1组XAF1蛋白表达率比较,差异无统计学意义(P>0.05);CIN2-3组及宫颈癌组XAF1蛋白表达率比较,差异均有统计学意义(P<0.05);正常宫颈组、CIN1组、CIN2-3组、宫颈癌组的BNIP3蛋白表达率分别为63.3%、70.0%、43.8%、14.6%,正常宫颈组与CIN1组BNIP3蛋白表达率比较,差异无统计学意义(P>0.05);CIN1组与CIN2-3组、宫颈癌组比较,BNIP3蛋白表达率逐渐下降,差异均有统计学意义(P<0.05);宫颈癌组织中XAF1蛋白与BNIP3蛋白表达呈正相关(P<0.05)。结论XAF1及BNIP3基因启动子甲基化所致的XAF1及BNIP3表达失活,可能在宫颈病变的发生及发展过程中起着重要作用。

Objective To investigate the relationship between the expression and abnormal methylation of tumor suppressor genes XAFl and BNIP3 and cervical lesions.Methods A total of 140 surgically resected specimens were selected,including 48 cases of cervical cancer group,32 cases of cervical intraepithelial neoplasia(CIN2-3 group),30 cases of cervical intradermal neoplasia(CIN1 group)and 30 cases of normal cervical tissue(control group).Methylation-specific polymerase chain reaction(MsP)and immunohistochemical(SP)methods were used to detect the methylation status and protein expression levels of XAF1 and BNIP3 promoter in the above groups.Results The positive rates of XAF1 promoter methylation in normal cervical group,CIN1 group,CIN2-3 group and cervical cancer group were 3.3%,6.6%,37.5%and 60.4%,respectively.There was no significant difference between normal cervical group and CIN1 group(P>0.05).There were significant differences in the methylation positive rate between CIN1 group,CIN2-3 group and cervical cancer group(P<0.05).The positive rates of BNIP3 gene methylation in normal cervical group,CIN1 group,CIN2-3 group and cervical cancer group were 16.7%,20.0%,43.8%and 68.8%,respectively.There was no significant difference between normal cervical group and CIN1 group(P>0.05).There were significant differences in the methylation positive rate between CINl group,CIN2-3 group and cervical cancer group(P<0.05).The positive expression rates of XAFl protein in normal cervical group,CIN1 group,CIN2-3 group and cervical cancer group were 73.3%,76.7%,40.6%and 10.4%,respectively.There was no significant difference between cervical group and CIN1 group(P>0.05).There were significant differences in XAF1 protein expression between CIN2-3 group and cervical cancer group(all P<0.05).The expression rates of BNIP3 protein in normal cervical group,CIN1 group,CIN2-3 group and cervical cancer group were 63.3%,70.0%,43.8%and 14.6%,respectively.There was no significant difference between normal cervical group and CIN1 group(P>0.05).The expression rate of BNIP3 protein in CIN1 group decreased gradually compared with CIN2-3 group and cervical cancer group,and the differences were statistically significant(P<0.05).There was a positive correlation between XAF1 protein and BNIP3 protein expression in cervical cancer tissues(P<0.05).Conclusion The deactivation of XAF1 and BNIP3 expression caused by XAF1 and BNIP3 gene promoter methylation may play an important role in the occurrence and development ofcervical lesions.