摘要
目的基于生物信息学分析胃腺癌组织中微小RNA(miRNA)差异表达情况,寻找可作为胃腺癌生物标记物的miRNA。方法利用癌症基因组图谱(TCGA)数据库下载胃腺癌相关数据集,分析肿瘤组织与正常组织之间miRNA的表达差异。利用Kaplan-Meier曲线进行患者生存分析,筛选具有潜在生物标记物性质(高表达、预后差)的miRNA。利用生物信息学预测miRNA的靶基因,通过基因本体(GO)和京都基因与基因组百科全书(KEGG)进行基因富集分析,以判定差异基因主要影响的生物学功能或者通路。结果 TCGA数据库分析结果发现,相对于45份正常组织,446份胃腺癌组织中存在319个差异表达miRNA,其中下调95个、上调224个。进一步通过生存分析筛选出6个高表达、与预后有关的miRNA(miR-217、miR-216a、miR-200b、miR-1911、miR-675、miR-96),其中miR-217高表达者预后差。胃腺癌组织中miR-217表达量为303.2±55.16,高于正常组织中的84.82±13.42(P<0.001)。通过Targetscan和miRDB生物信息预测软件对miR-217潜在靶基因取交集,获得151个有效靶基因;GO和KEGG分析结果显示,miR-217的这些靶基因与调节细胞凋亡、细胞周期、大分子代谢、蛋白酶的活性密切相关。结论利用生物信息学分析发现,与正常组织比较,胃腺癌组织中存在miRNA的差异表达;其中miR-217在胃腺癌组织中表达上调,通过调控靶基因参与相关的信号通路而导致患者预后不良,可成为胃腺癌的生物标记物。
Objective To analyze the differential expression of microRNAs（miRNAs） based on the bioinformatics to find miRNAs that can be used as biomarkers of gastric adenocarcinoma.Methods The data of gastric adenocarcinoma was downloaded from the Cancer Genome Atlas（TCGA） database to analyze the difference of miRNA expression between tumor tissues and normal tissues.Kaplan-Meier curves were used to perform patients＇ survival analysis to screen out the miRNAs with potential biomarker properties.Bioinformatics was used to predict the target genes of miRNAs,and gene enrichment analysis was performed through gene ontology（GO） and Kyoto Encyclopedia of Genomics（KEGG） to determine the biological functions or pathways which were mainly affected by differential genes.Results There were 319 differentially expressed miRNAs in 446 cases of gastric adenocarcinoma tissues as compared with 45 cases of the normal tissues,of which,95 were down-regulated and 224 were up-regulated.Six further miRNAs（miR-217,miR-216 a,miR-200 b,miR-1911,miR-675,miR-96） were screened out by survival analysis and subsequently selected for miR-217.Among them,patients with miR-217 overexpression had poor prognosis.The expression of miR-217 in the gastric adenocarcinoma was 303.2 ±55.16,which was higher than that（84.82 ± 13.42） in the normal tissues（P 〈 0.001）.Targetscan and miRDB bioinformatics software were used to predict the potential target genes of miR-217,and 151 valid genes were obtained.The results of GO and KEGG showed that these target genes of miR-217 were related to the regulation of apoptosis,cell cycle,macromolecular metabolism,and protease activity.Conclusions The bioinformatics analysis shows that compared with normal tissues,miRNAs are differentially expressed in the gastric adenocarcinoma.Among them,miR-217 is up-regulated in the gastric adenocarcinoma,which is involved in the relevant signaling pathway and leads to the poor prognosis of patients by regulating the target genes,and can be used as a biomarker of gastric adenocarcinoma.
作者
赵兰
何林秀
江龙洋
王昕楠
魏敏杰
赵琳
ZHAO Lan;HE Linxiu;JIANG Longyang;WANG Xinnan;WEI Minjie;ZHAO Lin(College of Pharmacy, China Medical University, Shenyang 110122, China)
出处
《山东医药》
CAS
2018年第2期21-24,共4页
Shandong Medical Journal
基金
国家自然科学基金资助项目(81703560)
辽宁省教育厅一般项目(LK201618)
辽宁省科技计划项目(2014226033)
辽宁省沈阳市科技计划项目(17-123-9-00)
辽宁省沈阳市科技计划项目重点实验室专项(F16-094-1-00)
关键词
胃腺癌
生物信息学分析
癌症基因组图谱
微小RNA
靶基因
预后
gastric adenocarcinoma
bioinformatics analysis
The Cancer Genome Atlas
microRNA
target gene
prognosis
