结直肠癌miRNA标志物的生信分析、鉴定及临床意义  

Bioinformatic analysis、identification and clinical significance of miRNA markers in colorectal cancer

作　　者：闫锴 邓鑫 YAN Kai;DENG Xin(Pharmacy Department of the Second People's Hospital of Meishan,Meishan 620500,China;Pharmaceutical Research Center,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]眉山市第二人民医院药剂科,四川眉山620500 [2]西南医科大学药物研究中心,四川泸州646000

出　　处：《黑龙江医药科学》2025年第2期68-72,76,共6页Heilongjiang Medicine and Pharmacy

摘　　要：目的:本研究旨在运用生物信息学方法,识别结直肠癌(colorectal cancer,CRC)中的差异表达miRNAs,并分析鉴定其靶基因中的核心基因(Hub基因),进一步探讨这些Hub基因在CRC中的表达及其与预后的关系,以期为CRC的研究提供新的分子靶点。方法:以CRC为关键词,在GEO数据库中检索并下载miRNA芯片数据集GSE35982和GSE128446。利用R语言的limma包对这两个数据集进行差异miRNAs分析,分别筛选出差异显著性排名前10的miRNAs,并通过venn图分析确定共有的差异miRNAs。然后利用targetscan、miranda、miwalk等工具预测并分析获得共有靶基因。通过String数据库构建蛋白互作网络(PPI),并使用Cytoscape软件进行可视化处理,结合CytoHubba插件确定前10位的Hub基因。随后,利用DAVID数据库对基因集进行GO功能和KEGG通路富集分析。最后,使用GEPIA 2软件分析Hub基因在CRC中的表达情况及其与患者生存的关系。结果:研究确定miR-135b为两个芯片数据集中差异最显著的前10位miRNAs的共有差异基因。对miR-135b的靶基因进行富集分析,结果显示这些基因主要参与多能性干细胞调控、Hippo、TGF-beta等信号通路。通过CytoHubba插件确定了RUNX2、KLF4、FOXO1、SP7、BGLAP、SMAD5、TGFBR1、MYC、BIRC5、PPP2R5C为Hub基因。KEGG分析显示,这些Hub基因主要与癌症通路、结直肠癌、TGF-beta信号通路相关。基因表达分析结果显示,BIRC5和MYC在CRC中高表达,而BGLAP和KLF4在CRC中低表达,RUNX2、FOXO1、SP7、SMAD5、TGFBR1、PPP2R5C在CRC中的表达无显著性差异(P>0.05)。生存分析显示,只有低表达的BGLAP基因与CRC患者的生存率显著相关(P<0.05)。结论:本研究筛选并确定了miR-135b是CRC中的关键差异miRNA。通过对其靶基因的预测、Hub基因的发掘、表达验证以及生存率分析,揭示了miR-135b及其靶基因网络调控CRC的可能机制。同时,研究还发现了参与CRC调控的潜在重要基因,为后续揭示CRC新�Objective:This study aims to identify differentially expressed miRNAs in colorectal cancer(CRC)using bioinformatics methods,analyze and identify core genes(Hub genes)among their target genes,and further explore the expression of these Hub genes in CRC and their relationship with prognosis,in order to provide new molecular targets for CRC research.Methods:With CRC as the keyword,miRNA microarray datasets GSE35982 and GSE128446 were retrieved and downloaded from the GEO database.The limma package in R language was used to analyze the differentially expressed miRNAs in these two datasets,and the top ten miRNAs with the most significant differences were selected.Venn diagram analysis was performed to identify common differentially expressed miRNAs.Subsequently,tools such as TargetScan,miRanda and miWalk were used to predict and analyze common target genes.The protein-protein interaction network(PPI)was constructed using the String database,and Cytoscape software was used for visualization.The CytoHubba plugin was employed to determine the top ten Hub genes.The DAVID database was then used for GO function and KEGG pathway enrichment analysis of the gene set.Finally,GEPIA 2 software was used to analyze the expression of Hub genes in CRC and their relationship with patient survival.Results:The study identified miR-135b as a common differentially expressed gene among the top ten miRNAs with the most significant differences in the two microarray datasets.Enrichment analysis of the target genes of miR-135b revealed that these genes are mainly involved in signaling pathways such as pluripotency stem cell regulation,Hippo and TGF-beta.The CytoHubba plugin identified RUNX2,KLF4,FOXO1,SP7,BGLAP,SMAD5,TGFBR1,MYC,BIRC5 and PPP2R5C as Hub genes.KEGG analysis showed that these Hub genes are mainly related to cancer pathways,colorectal cancer,and the TGF-beta signaling pathway.Gene expression analysis results indicated that BIRC5 and MYC are highly expressed in CRC,while BGLAP and KLF4 are lowly expressed in CRC.RUNX2,FOXO1,SP7,SMA

关 键 词：CRC MIRNA 生物信息学 靶基因 GEO 

分 类 号：R735.35[医药卫生—肿瘤]