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通过mRNA和miRNA微阵列数据的综合分析鉴定肝内胆管癌的生物标志物

Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data.

作者信息

Chen Yaqing, Liu Dan, Liu Pengfei, Chen Yajing, Yu Huiling, Zhang Quan

机构信息

Department of VIP Ward, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China.

Department of Ultrasonic Imaging, Zhuhai People's Hospital, Zhuhai, Guangdong 519000, P.R. China.

出版信息

Mol Med Rep. 2017 Mar;15(3):1051-1056. doi: 10.3892/mmr.2017.6123. Epub 2017 Jan 16.

Abstract

The present study aimed to identify potential therapeutic targets of intrahepatic cholangiocarcinoma (ICC) via integrated analysis of gene (transcript version) and microRNA (miRNA/miR) expression. The miRNA microarray dataset GSE32957 contained miRNA expression data from 16 ICC, 7 mixed type of combined hepatocellular‑cholangiocarcinoma (CHC), 2 hepatic adenoma, 3 focal nodular hyperplasia (FNH) and 5 healthy liver tissue samples, and 2 cholangiocarcinoma cell lines. In addition, the mRNA microarray dataset GSE32879 contained mRNA expression data from 16 ICC, 7 CHC, 2 hepatic adenoma, 5 FNH and 7 healthy liver tissue samples. The datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) in ICC samples compared with healthy liver tissues were identified via the limma package, following data preprocessing. Genes that exhibited alternative splicing (AS) in ICC samples were identified via AltAnalyze software. Functional enrichment analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis. Target genes of DEMs were identified using the TargetScan database. The regulatory association between DEMs and any overlaps among DEGs, alternative splicing genes (ASGs) and target genes of DEMs were retrieved, and a network was visualized using the Cytoscape software. A total of 2,327 DEGs, 70 DEMs and 623 ASGs were obtained. Functional enrichment analysis indicated that DEGs were primarily enriched in biological processes and pathways associated with cell activity or the immune system. A total of 63 overlaps were obtained among DEGs, ASGs and target genes of DEMs, and a regulation network that contained 243 miRNA‑gene regulation pairs was constructed between these overlaps and DEMs. The overlapped genes, including sprouty‑related EVH1 domain containing 1, protein phosphate 1 regulatory subunit 12A, chromosome 20 open reading frame 194, and DEMs, including hsa‑miR‑96, hsa‑miR‑1 and hsa‑miR‑25, may be potential therapeutic targets for the future treatment of ICC.

摘要

本研究旨在通过对基因(转录本版本)和微小RNA(miRNA/miR)表达的综合分析,确定肝内胆管癌(ICC)的潜在治疗靶点。miRNA微阵列数据集GSE32957包含来自16例ICC、7例混合型肝细胞-胆管癌(CHC)、2例肝腺瘤、3例局灶性结节性增生(FNH)和5例健康肝组织样本以及2株胆管癌细胞系的miRNA表达数据。此外,mRNA微阵列数据集GSE32879包含来自16例ICC、7例CHC、2例肝腺瘤、5例FNH和7例健康肝组织样本的mRNA表达数据。这些数据集从基因表达综合数据库下载。在数据预处理后,通过limma软件包鉴定与健康肝组织相比,ICC样本中的差异表达基因(DEG)和微小RNA(DEM)。通过AltAnalyze软件鉴定ICC样本中表现出可变剪接(AS)的基因。使用注释、可视化和综合分析数据库对DEG进行功能富集分析。使用TargetScan数据库鉴定DEM的靶基因。检索DEM与DEG、可变剪接基因(ASG)及DEM靶基因之间的重叠部分的调控关联,并使用Cytoscape软件将网络可视化。共获得2327个DEG、70个DEM和623个ASG。功能富集分析表明,DEG主要富集于与细胞活性或免疫系统相关的生物学过程和途径。在DEG、ASG和DEM靶基因之间共获得63个重叠部分,并在这些重叠部分和DEM之间构建了一个包含243个miRNA-基因调控对的调控网络。重叠基因包括含sprouty相关EVH1结构域蛋白1、蛋白磷酸酶1调节亚基12A、20号染色体开放阅读框194,以及DEM,包括hsa-miR-96、hsa-miR-1和hsa-miR-25,可能是未来ICC治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cc9/5367350/8139a69ee41f/MMR-15-03-1051-g00.jpg

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