胃癌预后全基因组关联分析

Gastric cancer prognosis-related single nucleotide polymorphisms:a genome-wide association analysis

目的探讨胃癌预后相关的全基因组单核苷酸多态性(SNPs)位点,为识别胃癌预后生物标志物、开发个性化胃癌治疗策略提供新的思路。方法对2013年4月—2017年12月在福建省仙游县医院新确诊的251例胃癌患者进行随访研究,采用Kaplan-Meier法计算5年生存率,通过全基因组芯片检测胃癌患者的全基因组SNPs位点,并应用Cox比例风险回归模型探索胃癌预后相关的SNPs位点。结果有效随访胃癌患者218例,随访率为86.85%,1、3、5年生存率分别为61.5%、40.8%、37.5%,中位生存期为22.0个月;单因素Cox比例风险回归模型分析结果显示,年龄≥65岁、TNM分期中期和晚期是胃癌预后不良的危险因素,接受手术治疗和化疗治疗为胃癌预后不良的保护因素;胃癌预后的全基因组关联分析(GWAS)发现165个与胃癌预后存在全基因组显著性关联的遗传位点,涉及33个功能区域,对应55个功能基因,主要参与生长因子反应通路、免疫逃逸、炎性相关通路等生物过程,其中7个基因的表达在TCGA数据库中显示与胃癌预后显著相关。结论SNPs与胃癌预后紧密相关,胃癌预后功能基因广泛参与癌细胞增殖、免疫、炎症等生物过程。

Objective To explore the association of genome-wide single nucleotide polymorphisms(SNPs)with the prognosis of gastric cancer(GC)for identifying new prognostic biomarkers and developing personalized treatment strategies for GC.Methods A follow-up study was conducted among 251 first diagnosed GC patients recruited in a county hospital of Fujian province from April 2013 to December 2017.Kaplan-Meier method was used to calculate 5-year survival rate of the patients and genome-wide SNPs loci of the patients were detected with whole-genome chip.Cox proportional hazards regression model was applied to analyze the association of SNPs loci with GC prognosis.Results Of all the patients,218(86.85%)completed the follow-up and were included in the analysis.The 1-,3-,and 5-year survival rate of the patients were61.5%,40.8%,and 37.5%,respectively,and the median survival time was 22.0 months.Univariate Cox proportional hazards regression analysis showed that aged≥65 years and at intermediate and advanced tumor node metastasis(TNM)stage were risk factors for poor prognosis of GC;while,undergoing surgery and chemotherapy were protective factors against poor prognosis.The genome-wide association study(GWAS)identified 165 genetic loci significantly associated with GC prognosis,which involved 33 functional regions corresponding to 55 functional genes.The function genes were mainly involved in growth factor response pathway,immune escape,and inflammation-related pathways and the expression of 7 of functional genes correlated significantly with GC prognosis based on the information from The Cancer Genome Atlas(TCGA)database.Conclusion The SNPs are closely related to the prognosis of GC and the GC prognosis-related functional genes are widely involved in biological processes of cancer cell proliferation,immunity and inflammation.