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PRDM12FOXE1B3GAT2VIMSFRP2基因在结直肠癌组织中的甲基化水平
徐正1,2,颜宏利1*
0
(1. 海军军医大学(第二军医大学)长海医院生殖医学中心, 上海 200433;
2. 上海中医药大学附属第七人民医院检验科, 上海 200137
*通信作者)
摘要:
目的 检测结直肠癌组织中PR结构域蛋白12(PRDM12)、叉头框E1(FOXE1)、β-1,3-葡糖醛转移酶2(B3GAT2)、波形蛋白(VIM)、分泌型卷曲相关蛋白2(SFRP2)基因的甲基化水平,初步评估上述基因作为结直肠癌早期筛查标志物的潜力。方法 选取海军军医大学(第二军医大学)长海医院31例接受手术切除治疗的结直肠癌患者的石蜡切片标本,使用焦磷酸测序法检测癌组织和相应癌旁正常组织中PRDM12FOXE1B3GAT2VIMSFRP2-1SFRP2-2基因启动子的甲基化水平。结果 31例结直肠癌患者癌组织中PRDM12FOXE1B3GAT2VIMSFRP2-1SFRP2-2基因启动子甲基化指数均高于相应癌旁正常组织,差异均有统计学意义(P均<0.01)。在31例结直肠癌患者中,PRDM12FOXE1B3GAT2VIMSFRP2-1SFRP2-2基因启动子高度甲基化率分别为87.1%(27/31)、90.3%(28/31)、80.6%(25/31)、77.4%(24/31)、74.2%(23/31)、64.5%(20/31);在18例早期(TNMⅠ~Ⅱ期)结直肠癌患者中,PRDM12FOXE1B3GAT2VIMSFRP2-1SFRP2-2基因启动子高度甲基化率分别为88.9%(16/18)、94.4%(17/18)、83.3%(15/18)、77.8%(14/18)、83.3%(15/18)、61.1%(11/18)。结论 PRDM12FOXE1基因在结直肠癌组织中出现异常甲基化,初步判断两者有潜力成为结直肠癌早期筛查的分子标志物。
关键词:  焦磷酸测序  PR结构域蛋白12  叉头框E1  DNA甲基化  结直肠肿瘤
DOI:10.16781/j.0258-879x.2020.10.1169
投稿时间:2020-05-13修订日期:2020-10-12
基金项目:国家自然科学基金(81672350),上海市浦东新区卫生和计划生育委员会重要薄弱学科建设项目(PWZbr2017-01).
Methylation status of PRDM12, FOXE1, B3GAT2, VIM and SFRP2 genes in colorectal cancer
XU Zheng1,2,YAN Hong-li1*
(1. Department of Reproductive Medicine, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Clinical Laboratory, Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
*Corresponding author)
Abstract:
Objective To detect the methylation levels of PR domain-containing protein 12 (PRDM12), forkhead box E1 (FOXE1), beta-1,3-glucuronyltransferase 2 (B3GAT2), vimentin (VIM) and secreted frizzled-related protein 2 (SFRP2) genes in colorectal cancer tissues, so as to evaluate their potentials as early screening markers for colorectal cancer. Methods The paraffin specimen samples were collected from 31 colorectal cancer patients receiving surgical resection in Changhai Hospital, Naval Medical University (Second Military Medical University). The methylation levels of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 gene promoters in cancer tissues and corresponding paracancerous normal tissues were detected using pyrosequencing method. Results The promoter methylation indexes of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 genes were significantly higher in the cancer tissues of the 31 patients than those in the paracancerous tissues (all P<0.01). The positive methylation rates of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 gene promoters were 87.1% (27/31), 90.3 (28/31), 80.6% (25/31), 77.4% (24/31), 74.2% (23/31) and 64.5% (20/31), respectively. In the 18 cases of early stage (TNM Ⅰ-Ⅱ) colorectal cancer, the positive methylation rates of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 gene promoters were 88.9% (16/18), 94.4% (17/18), 83.3% (15/18), 77.8% (14/18), 83.3% (15/18) and 61.1% (11/18), respectively. Conclusion PRDM12 and FOXE1 genes show abnormal methylation in colorectal cancer tissues, suggesting that they may serve as potential molecular markers for the early diagnosis of colorectal cancer.
Key words:  pyrosequencing  PR domain-containing protein 12  forkhead box E1  DNA methylation  colorectal neoplasms