胃癌差异表达miRNA及其相关基因的单核苷酸多态性与胃癌预后的相关性研究

doi:10.3969/j.issn.1004-616x.2020.05.009

癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (5): 380-386.doi: 10.3969/j.issn.1004-616x.2020.05.009

胃癌差异表达miRNA及其相关基因的单核苷酸多态性与胃癌预后的相关性研究

吕燕萍¹, 吴传城¹, 杨双凤¹, 何陈周¹, 韩仁杰¹, 颜伟², 刘宝英¹

1. 福建医科大学公共卫生学院, 福建福州 350108;
2. 福建省莆田市仙游县总医院, 福建莆田 351200

收稿日期:2020-01-18 修回日期:2020-07-02 出版日期:2020-10-01 发布日期:2020-10-12
通讯作者: 刘宝英,E-mail:liuby5@126.com E-mail:liuby5@126.com
作者简介:吕燕萍,E-mail:1397546513@qq.com。
基金资助:
福建省自然科学基金（2015J01673，2017J01811）；福建省医学创新课题（2016-CX-41）

Relationship between differentially expressed miRNA-SNPs and prognosis of gastric cancer

Lü Yanping¹, WU Chuancheng¹, YANG Shuangfeng¹, HE Chenzhou¹, HAN Renjie¹, YAN Wei², LIU Baoying¹

1. School of Public Health, Fujian Medical University, Fuzhou 350108;
2. General Hospital of Xianyou County, Putian City, Fujian Province, Putian 351200, Fujian, China

Received:2020-01-18 Revised:2020-07-02 Online:2020-10-01 Published:2020-10-12

摘要/Abstract

摘要： 目的：探讨胃癌差异表达微小RNA（miRNA）及其相关基因的单核苷酸多态性（SNPs）与胃癌预后的相关性，为进一步寻找胃癌预后的生物标志物提供线索。方法：应用SNP芯片联合生物信息学分析对福建省胃癌高发区仙游县96例胃腺癌患者与96例健康对照人群基因组中miRNA及其相关基因的SNPs位点进行筛检，应用飞行时间质谱生物芯片（Sequenom MassARRAY）在344例胃癌患者中对筛检出来的SNPs位点进行检测。开展现场流行病学调查，通过面对面的访谈及问卷调查取得患者的病情、治疗方法、患病后1年的生活饮食习惯，分析其预后情况。结果：共筛检出11个miRNA及其相关基因的SNPs位点，包括5个miRNA自身SNPs、5个miRNA靶序列SNPs以及1个miRNA生物合成通路基因相关SNPs。单因素分析显示miR-1297 rs9536676、MSH2 rs17502941位点的多态性与胃癌预后有关联性，其余的多态性位点均与胃癌预后无明显相关性。多因素分析显示是否手术、TNM分期、rs17502941 AA/AG基因型均是影响胃癌预后的独立危险因素。按年龄TNM分期联合分层得出，miR-1297 rs9536676、miRNA-519b rs10413288、miR-379 rs7143252、FAS基因rs1468063、EGFR基因rs10277413位点均与胃癌患者的生存分布有关联。联合作用分析结果显示患者同时携带rs9536676 AA/AG和rs17502941 GG、rs9536676 AA/AG和rs10413288 AA、rs17502941 GG和rs10413288 AA基因型可能会增加预后不良的风险（P < 0.05）。结论：胃癌差异表达miRNA及其相关基因的SNPs与胃癌病人预后密切相关，可能作为判断胃癌预后的生物标志物。

关键词: 微小RNA, 单核苷酸多态性, 胃癌, 预后

Abstract: OBJECTIVE: To explore relationships between differentially expressed miRNA-related single nucleotide polymorphism (SNPs) and the prognosis of gastric cancer,and to provide recommendations for molecular biomarkers for prognosis of gastric cancer. METHODS: Eleven differentially expressed miRNA-SNPs of gastric cancer were selected as gene loci by SNP microarray and bioinformatics methods. Single nucleotide polymorphisms (SNPs) of total DNA in peripheral blood leukocytes of 344 patients with gastric cancer were detected by Sequenom MassARRAY. An on the spot face to face interview was carried out to collect information on patient's condition,treatment,living and eating habits for one year after the illness. The information and survival analyses were used to study relationships between miRNA-related SNPs and prognosis of gastric cancer. RESULTS: Univariate analyses showed that the polymorphisms of rs9536676 of miR-1297 and rs17502941 of MSH2 were associated with the prognosis of gastric cancer,while the other polymorphisms had no significant association. Multivariate analyses showed that surgery,TNM stage and rs17502941 AA/AG genotype were independent risk factors for the prognosis of gastric cancer. According to stratification by age and TNM stages,rs9536676 of miR-1297,rs10413288 of miRNA-519b,rs7143252 of miR-379,rs1468063 of FAS and rs10277413 of EGFR were significantly associated with the survival distribution of patients with gastric cancer. The results showed that patients with rs9536676 AA/AG and rs17502941 GG,rs9536676 AA/AG and rs10413288 AA,rs17502941 GG and rs10413288 AA genotypes had increased risk of poor prognosis. CONCLUSION: The differential expression of certain miRNA-SNPs in gastric cancer was closely related to the prognosis of patients with gastric cancer. The association can be used to investigate mechanisms for predicting the prognosis.

Key words: microRNA, single nucleotide polymorphism, gastric cancer, prognosis

中图分类号:

R735.2

吕燕萍, 吴传城, 杨双凤, 何陈周, 韩仁杰, 颜伟, 刘宝英. 胃癌差异表达miRNA及其相关基因的单核苷酸多态性与胃癌预后的相关性研究[J]. 癌变·畸变·突变, 2020, 32(5): 380-386.

Lü Yanping, WU Chuancheng, YANG Shuangfeng, HE Chenzhou, HAN Renjie, YAN Wei, LIU Baoying. Relationship between differentially expressed miRNA-SNPs and prognosis of gastric cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 380-386.

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胃癌差异表达miRNA及其相关基因的单核苷酸多态性与胃癌预后的相关性研究

Relationship between differentially expressed miRNA-SNPs and prognosis of gastric cancer

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