胃癌患者FHIT、hMLH1、p16、RAR-beta、Reprimo和TIMP3基因的甲基化研究

doi:10.11904/j.issn.1002-3070.2019.01.002

实用肿瘤学杂志 ›› 2019, Vol. 33 ›› Issue (1): 8-13.doi: 10.11904/j.issn.1002-3070.2019.01.002

胃癌患者FHIT、hMLH1、p16、RAR-beta、Reprimo和TIMP3基因的甲基化研究

白玉贤, 马仲娟, 苏颖玲, 慕安国, 谢蕊

哈尔滨医科大学附属肿瘤医院消化肿瘤内科(哈尔滨 150081)

收稿日期:2017-11-27 出版日期:2019-02-28 发布日期:2019-02-13
通讯作者: 白玉贤,E-mail:bai_yuxian@126.com
作者简介:白玉贤,女,(1960-),博士,主任医师,从事消化道肿瘤分子靶向诊治的研究。
基金资助:
黑龙江省教育厅科学技术研究项目(编号:12541309)

Research on methylation of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in gastric cancer patients

BAI Yuxian, MA Zhongjuan, SU Yingling, MU Anguo, XIE Rui

Department of Digestive Oncology,Harbin Medical University Cancer Hospital,Harbin 150081,China

Received:2017-11-27 Online:2019-02-28 Published:2019-02-13

摘要/Abstract

摘要： 目的探究人脆性组氨酸三联体(FHIT)基因、人mut1同源物(hMLH1)基因、p16基因、维甲酸受体(RAR)-beta(RAR-beta)基因、Reprimo基因和基质金属蛋白酶抑制因子3(TIMP3)基因在胃癌及相应的癌旁对照组织中甲基化状态。方法采用亚硫酸氢钠测序法检测42例临床手术切除的胃癌标本及42例相应癌旁组织标本中FHIT基因、hMLH1基因、p16基因、RAR-beta基因、Reprimo基因和TIMP3基因甲基化水平。结果胃癌组织及相应癌旁组织之间各基因的平均甲基化率分别为:FHIT基因(1.50%,1.36%)、hMLH1基因(4.77%,0.48%)、p16基因(9.63%,10.36%)、RAR-beta基因(4.75%,4.17%)、Reprimo基因(9.71%,3.76%)与TIMP3基因(18.34%,14.06%)。癌旁对照组织与胃癌组织的Reprimo基因的平均甲基化率具有统计学差异(P＜0.05)。组织分化程度不同的胃癌患者Reprimo基因启动子甲基化率存在统计学差异(P＜0.05)。结论胃癌中Reprimo基因启动子区胞嘧啶鸟嘌呤二核苷酸岛中存在甲基化现象。Reprimo基因的高甲基化率可以作为胃癌的潜在生物标记物,以便早期发现胃癌。

关键词: 胃癌, 亚硫酸氢盐测序法, 甲基化, Reprimo基因

Abstract: Objective The aim of this study was to investigate the methylation status of fragile histidine triad(FHIT)gene,human mutl homolog 1(hMLH1)gene,p16 gene,retinoic acid receptor beta(RAR-beta)gene,Reprimo gene and tissue inhibitor of metalloproteinase 3(Timp3)gene in gastric cancer and corresponding paracancerous tissues.Methods The methylation levels of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in 42 clinically resected gastric cancer specimens and 42 corresponding paracancerous tissues were detected by sodium bisulfite sequencing.Results The average methylation rates of the genes in gastric cancer and corresponding paracancerous tissues were:FHIT(1.50%,1.36%),hMLH1(4.77%,0.48%),p16(9.63%,10.36%),RAR-beta(4.75%,4.17%),Reprimo(9.71%,3.76%)and TIMP3 genes(18.34%,14.06%).Compared with the paracancerous control group,the average methylation rate of Reprimo gene was only statistically different in gastric cancer patients(P=0.00787).The difference in methylation rate of Reprimo gene promoter in gastric cancer patients with the degree of tissue differentiation was statistically significant(P＜0.05).Conclusion There has methylation in the cytosine guanidine dinucleotide island of the Reprimo gene promoter region in gastric cancer.The high methylation rate of the Reprimo gene can be used as a potential biomarker for gastric cancer to detect the early stage of gastric cancer.

Key words: Gastric cancer, Bisulfite sequencing PCR method, Methylation, Reprimo gene

中图分类号:

R737.9

白玉贤, 马仲娟, 苏颖玲, 慕安国, 谢蕊. 胃癌患者FHIT、hMLH1、p16、RAR-beta、Reprimo和TIMP3基因的甲基化研究[J]. 实用肿瘤学杂志, 2019, 33(1): 8-13.

BAI Yuxian, MA Zhongjuan, SU Yingling, MU Anguo, XIE Rui. Research on methylation of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in gastric cancer patients[J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(1): 8-13.

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胃癌患者FHIT、hMLH1、p16、RAR-beta、Reprimo和TIMP3基因的甲基化研究

Research on methylation of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in gastric cancer patients

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