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通过大数据分析对肝细胞癌血管侵袭标志物进行生物信息学研究

[Bioinformatics on vascular invasion markers in hepatocellular carcinoma via Big-Data analysis].

作者信息

Chen Q, Qiu X Q

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning 530021, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2017 Apr 10;38(4):522-527. doi: 10.3760/cma.j.issn.0254-6450.2017.04.022.

DOI:10.3760/cma.j.issn.0254-6450.2017.04.022
PMID:28468075
Abstract

To investigate the biomarkers in hepatocellular carcinoma and their prognostic value via GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) database. Datasets of hepatocellular carcinoma were downloaded from GEO (GSE67140) and TCGA. MicroRNA in SNU423, SNU449, HepG2, Hep3B, SNU398 cell lines which had low or high invasion capabilities were investigated and verified, in 81 patients with and 91 without vascular invasion hepatocellular carcinoma. The prognostic value of these microRNAs were studied via TCGA database,obtained from 362 patients with hepatocellular carcinoma, through Kaplan-Meier and Multivariate Cox proportional hazard analysis. Target genes were analyzed by GO and KEGG. Expressions of hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were all up regulated in high invasion capable cell lines (SNU423, SNU449) and vascular invasion patients with hepatocellular carcinoma (logFC>1, <0.05). Results from the Survival analysis showed that hsa-mir-1180 (=1.623, 95: 1.114-2.365, =0.012), hsa-mir-149 (=2.400, 95: 1.639-3.514) and hsa-mir-940 (=1.704, 95: 1.188-2.443, =0.004) were independent risk factors on the prognosis of patients with hepatocellular carcinoma (<0.05). The mechanism might be related to factors as immune response, focal adhesion and adherence junction signaling pathways. With TCGA and GEO data mining, we found that hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were all highly related to the prognosis of hepatocellular carcinoma, that enabled it to be used to further study the biomarkers related to the prognosis of hepatocellular carcinoma.

摘要

通过基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库研究肝细胞癌中的生物标志物及其预后价值。从GEO(GSE67140)和TCGA下载肝细胞癌数据集。研究并验证了具有低侵袭能力或高侵袭能力的SNU423、SNU449、HepG2、Hep3B、SNU398细胞系中的微小RNA,以及81例有血管侵犯和91例无血管侵犯的肝细胞癌患者中的微小RNA。通过TCGA数据库,从362例肝细胞癌患者中获取数据,通过Kaplan-Meier法和多变量Cox比例风险分析研究这些微小RNA的预后价值。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析靶基因。hsa-mir-1180、hsa-mir-149、hsa-mir-744和hsa-mir-940在高侵袭能力细胞系(SNU423、SNU449)和有血管侵犯的肝细胞癌患者中均上调(logFC>1,P<0.05)。生存分析结果显示,hsa-mir-1180(HR = 1.623,95%CI:1.114 - 2.365,P = 0.012)、hsa-mir-149(HR = 2.400,95%CI:1.639 - 3.514)和hsa-mir-940(HR = 1.704,95%CI:1.188 - 2.443,P = 0.004)是肝细胞癌患者预后的独立危险因素(P<0.05)。其机制可能与免疫反应、粘着斑和紧密连接信号通路等因素有关。通过挖掘TCGA和GEO数据,我们发现hsa-mir-1180、hsa-mir-149、hsa-mir-744和hsa-mir-940均与肝细胞癌的预后高度相关,这使其能够用于进一步研究与肝细胞癌预后相关的生物标志物。

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