目的 探讨NBN基因3'端非编码区潜在的功能性单核苷酸多态性位点rs10464867遗传变异在胃癌易感性中的生物信息学功能.方法 利用生物信息学工具进行NBN基因生物信息学功能的预测和分析,并基于癌症基因组图谱计划(TCGA)数据库RNA-Seq的表达数据分析胃腺癌组织及癌旁组织中NBN mRNA的表达,初步推测NBN基因在胃癌发生中潜在存在的生物学功能.结果 在GTEx数据库中对与rs10464867高连锁不平衡(LD)的单核苷酸多态性(SNP)和NBN基因进行表达数量性状位点(eQTL)分析,结果发现rs2284135与NBN基因存在eQTL,rs2284135的A等位基因可以显著增加NBN基因的表达(P＜0.05).根据TCGA数据库RNA-Seq表达数据分析也进一步显示NBNmRNA在胃腺癌组织中的表达水平显著高于癌旁正常组织(P＜0.01).结论 NBN基因rs10464867与胃癌风险相关,可能通过eQTL位点rs2284135来调控NBN基因的表达,在胃癌发生发展中发挥生物学功能,从而影响胃癌患病风险,生物信息学功能预测也有助于进一步认识NBN基因在肿瘤发生发展中的作用.%Objective To analyse the biological functionof the potentially functional single nucleotide polymorphisms (SNPs) rs10464867 in the 3'-untranslated region of NBN gene with gastric cancer risk.Methods The potentially biological function was predicted and analysed with RegulomeDB,University of California Santa Cruz (UCSC),HaploReg and The genotype tissue expression (GTEx) database.We also performed differential expressed analysis of NBN mRNA expression level with RNA-Seq data of paired gastric adenocarcinoma tissues from The Cancer Genome Atlas (TCGA).Results Functional annotation analysis based on GTEx revealed that rs2284135,which is in perfect Linkage Disequilibrium (LD) (r2 =0.98) with rs10464867,is an eQTL loci of NBN.rs2284135 A allele can significantly increase the expression of NBN gene in whole blood (beta =0.31,P ＜ 0.05).Differential expressed analysis of NBN gene based on TCGA RNA-Seq data further revealed that the expression level of NBN mRNA-was significantly higher in gastric adenocarcinoma tissues than adjacent normal tissues (P ＜ 0.01).Conclusion In this current study,we found thatrs10464867,located in the 3'TUR ofNBN gene was a new independent susceptibility variant of gastric cancer in Chinese,providing important clues that genetic variants in NBN might also involve in the susceptibility of gastric cancer and further highlight the potentiallypleiotropic effect of NBN SNPs on multiple cancers.It also provids clues to clarify the gastric cancer pathogenic mechanisms of the functional loci at NBN gene.
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