宫颈癌APC基因启动子甲基化与其临床病理特征的关系

Promoter methylation of APC genes in cervical cancer:correlation with clinicopathologic characteristics

背景与目的:腺瘤性结肠息肉病(adenomatous polyposis coli,APC@基因是Wnt信号传导通路中重要的抑癌基因,其启动子区CpG岛高甲基化引起的基因失活可导致Wnt信号传导通路异常,与多种肿瘤有关。APC基因启动子甲基化与宫颈癌的关系研究较少。本研究检测宫颈癌标本中APC基因启动子甲基化状态,并分析其与临床病理特征及高危型人乳头瘤病毒(HPV@感染的关系,探讨APC基因启动子甲基化与宫颈癌的关系。方法:运用甲基化特异性PCR(MSP@检测95例宫颈癌标本及对照组20例正常宫颈组织的APC基因启动子甲基化状态,并分析APC基因甲基化状态与不同临床病理特征及高危型HPV感染之间的联系。结果:宫颈癌组APC基因甲基化率明显高于正常对照组(分别为56.8%,10%,P<0.01@。宫颈癌APC基因甲基化检测和高危型HPV DNA检测结果有较好的一致性(Kappa=0.348,P<0.001@。腺癌组甲基化率较鳞癌组高(分别为74.1%,50.0%,P<0.05@。APC甲基化阳性率随肿块增大及淋巴结转移而增高(P<0.05@。不同年龄、FIGO临床分期、WHO病理分级、肿瘤侵犯深度和APC基因甲基化未见明显关系(P>0.05@。结论:宫颈癌APC基因启动子甲基化与高危型HPV具有良好的一致性。APC基因启动子高甲基化为频发事件,并与不同宫颈癌病理类型相关,可作为宫颈癌诊断及分型的生物学标志物。

Background and purpose：The Wnt cell-signaling pathway is the key cellular developmental pathway.Dysregulation of this pathway has been implicated in the initiation and progression of cancer.Adenomatous polyposis coli（APC）is an important tumor suppressor gene of the Wnt signaling pathway.The methylation of APC promoter and the accompanying loss of the APC transcript have been shown to occur in a signifi cant proportion of cancers.However,there are few reports on the relationship between cervical cancer and methylation of APC.This study was aimed to investigate the promoter methylation status of the APC genes in cervical cancer and its correlation between clinicopathologic characteristics and the infection of high-risk HPV DNA.Methods：Promoter methylation was evaluated using a MSP（methylation-specifi c polymerase chain reaction）in 95 cervical cancer tissue specimens and 20 normal controls.The relationship between clinicopathologic parameters and the methylation status was evaluated.Results：The frequencies of promoter methylation of APC in cervical cancer were 56.8%.Cervical cancer had significant higher methylation frequencies than that of the controls（10%,P0.01）.The result showed that the methylation analysis of APC promoter and high-risk HPV DNA testing had good consistency（Kappa=0.348,P0.001）.The promoter methylation of APC was signifi cantly higher in adenocarcinoma（AC）than in squamous cell carcinoma（SCC）（74.1% vs 50.0%,respectively,P0.05）.The larger tumor size,positive lymph node metastasis and positiveHPV DNA exhibited an increased promoter methylation frequency for APC（P0.05）.There were no significant associations between the methylation frequencies for APC gene to age,invasion depth,FIGO stage and histological grade.Conclusion：Our results suggested that the promoter methylation of APC and high-risk HPV DNA testing had good consistency.APC gene promoter methylation was a frequent epigenetic event in cervical carcinoma and had a signifi cant correlation with cancer pathological types.