Yuan Min, Yao Lili, Abulizi Guzhalinuer
Department of Gynaecology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, P.R. China.
Medicine (Baltimore). 2019 Sep;98(38):e17225. doi: 10.1097/MD.0000000000017225.
The present study is to analyze the difference of gene methylation in early cervical adenocarcinoma and to find molecular markers for predicting the occurrence and development of cervical adenocarcinoma.A total of 15 cases of primary cervical adenocarcinoma and 10 cases of primary cervical squamous cell carcinoma at stages IB1 or IIA1 were included in the study. Infinium MethylationEPIC BeadChip (850K) was used to screen specifically expressed genes in cervical adenocarcinoma tissues. Bisulfite sequencing polymerase chain reaction (BSP) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the methylation levels in cervical adenocarcinoma, cervical squamous cell carcinoma, and normal cervical tissues.Sex determining region Y-box 1 (SOX1) and cyclin D1 (CCND1) genes participated in multiple signaling pathways, being the central nodes of gene regulatory networks. SOX1 gene, but not CCND1 gene, was a specifically methylated gene in cervical adenocarcinoma according to BSP. According to qRT-PCR, methylation level of SOX1 in cervical adenocarcinoma tissues is significantly different from that in cervical squamous cell carcinoma tissues or normal cervical tissues, and the methylation level of CCND1 in cervical adenocarcinoma tissues or cervical squamous cell carcinoma tissues is significantly different from that in normal cervical tissues.The present study demonstrates that tumor-suppressor gene SOX1 is a methylation-specific expression gene of cervical adenocarcinoma and is expected to become a specific molecular marker for the diagnosis of cervical adenocarcinoma. However, CCND1 gene was not proven to be a specific methylation expression gene in cervical adenocarcinoma in the present study.
本研究旨在分析早期宫颈腺癌中基因甲基化的差异,并寻找预测宫颈腺癌发生发展的分子标志物。本研究共纳入15例IB1期或IIA1期原发性宫颈腺癌和10例原发性宫颈鳞状细胞癌。采用Infinium MethylationEPIC BeadChip(850K)筛选宫颈腺癌组织中的特异性表达基因。采用亚硫酸氢盐测序聚合酶链反应(BSP)和定量实时聚合酶链反应(qRT-PCR)验证宫颈腺癌、宫颈鳞状细胞癌和正常宫颈组织中的甲基化水平。性别决定区Y盒1(SOX1)和细胞周期蛋白D1(CCND1)基因参与多个信号通路,是基因调控网络的中心节点。根据BSP结果,SOX1基因而非CCND1基因是宫颈腺癌中的特异性甲基化基因。根据qRT-PCR结果,宫颈腺癌组织中SOX1的甲基化水平与宫颈鳞状细胞癌组织或正常宫颈组织中的甲基化水平有显著差异,宫颈腺癌组织或宫颈鳞状细胞癌组织中CCND1的甲基化水平与正常宫颈组织中的甲基化水平有显著差异。本研究表明,抑癌基因SOX1是宫颈腺癌的甲基化特异性表达基因,有望成为诊断宫颈腺癌的特异性分子标志物。然而,在本研究中,CCND1基因未被证明是宫颈腺癌中的特异性甲基化表达基因。