宫颈癌组织ITIH5基因启动子及第1外显子甲基化状态与其临床病理特征关系的研究  

Study the methylation status of ITIH5 gene promoter and exon 1 in cervical cancer:correlation with clinicopathologic characteristics

作　　者：仵妍[1] 毕晓宁[2] 王言奎[2] 

机构地区：[1]青岛大学医学院附属海慈医院妇产科,青岛266003 [2]青岛大学附属医院妇产科,青岛266011

出　　处：《现代妇产科进展》2015年第4期247-250,共4页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:81172480)

摘　　要：目的:探讨宫颈癌组织中人类间胰蛋白酶H5重链(ITIH5)基因启动子及第1外显子区甲基化状态对ITIH5表达的影响,分析ITIH5基因甲基化程度与临床病理特征的关系。方法:选取50例宫颈癌组织和20例正常宫颈组织作为研究对象,采用甲基化特异PCR(MSP)和亚硫酸盐基因组测序法(BGS)检测ITIH5基因启动子及第1外显子区甲基化状态,采用实时荧光定量PCR(qRT-PCR)法检测ITIH5 mRNA表达。结果:宫颈癌组织中ITIH5基因甲基化率明显高于正常宫颈组织(χ2=16.104,P=0.000),ITIH5 mRNA表达量明显低于正常宫颈组织(t=3.640,P=0.001)。宫颈癌组织中ITIH5甲基化率与淋巴结转移密切相关(校正χ2=4.562,P=0.029),而与临床分期、组织病理学分级、脉管浸润、深肌层浸润、病理类型之间无显著相关性(P>0.05)。结论:ITIH5基因启动子及第1外显子区Cp G岛的高甲基化可能是宫颈癌组织ITIH5基因表达降低甚至沉默的原因。ITIH5基因可能成为宫颈癌的候选抑癌基因,可能与宫颈癌的发生和淋巴结转移有关。Objective：To investigate the promoter and exon 1 methylation status of the ITIH5 gene in cervical cancer and its correlation with clinicopathologic characteristics. Meth-ods：The methylation status of ITIH5 promoter and exon 1 were evaluated by MSP（ methylation-specific polymerase chain reaction ） and BGS （ bisulfite genome sequencing ） in 50 cervical cancer tissues and 20 normal cervical tissues. ITIH5 gene mRNA expression was detected by qRT-PCR. Results：The methylation rate of ITIH5 gene in cervical cancer was significantly higher than that in normal cervical tissues（χ2=16. 104,P=0. 000）. Higher methylation rate in cervical cancer was associated with regional lymph node invasion （ continuous correction χ2=4. 562,P=0. 029）,while there were no significant associations with clinical stage,histological grade and types of pathology （ P〉0 . 05 ） . The mRNA expression was lower in cervical cancer compared with normal cervical tissues（t=3. 640,P=0. 001）. Conclusion：ITIH5 gene promot-er and exon1 hypermethylation is a frequent event in cervical tissues and may lead to the loss of mRNA expression. ITIH5 gene may be a candidate suppressor gene of cervical cancer,and may be associated with the tumorigenesis and lymphatic metastasis of cervical cancer.

关 键 词：TIH5 宫颈癌 甲基化 

分 类 号：R737.33[医药卫生—肿瘤]