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肝硬化转化为肝细胞癌关键基因和通路的生物信息学分析

Bioinformatics analysis of key genes and pathways for hepatocellular carcinoma transformed from cirrhosis.

作者信息

He Bosheng, Yin Jianbing, Gong Shenchu, Gu Jinhua, Xiao Jing, Shi Weixiang, Ding Wenbin, He Ying

机构信息

Department of Radiology, the Second Affiliated Hospital of Nantong University Department of Pathophysiology, Nantong University Medical School Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University Department of Ultrasound, the Tumor Hospital of Nantong University, Nantong, Jiangsu, China.

出版信息

Medicine (Baltimore). 2017 Jun;96(25):e6938. doi: 10.1097/MD.0000000000006938.

Abstract

OBJECTIVE

We aimed to identify some pivotal genes and pathways for hepatocellular carcinoma (HCC) transformation from cirrhosis and explore potential targets for treatment of the disease.

METHODS

The GSE17548 microarray data were downloaded from Gene Expression Omnibus database, and 37 samples (20 cirrhosis and 17 HCC samples) were used for analysis. The differentially expressed genes (DEGs) in HCC tissues were compared with those in cirrhosis tissues and analyzed using the limma package. Gene ontology-biological process and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using ClueGO and CluePedia tool kits, and the key KEGG pathway was analyzed using the R package pathview. The regulatory factor miRNA of DEGs was extracted from 3 verified miRNAs-target databases using the multiMiR R package. Moreover, a protein-protein interaction (PPI) network was constructed using the Cytoscape software.

RESULTS

DEGs including cyclin-dependent Kinase 1 (CDK1), PDZ-binding kinase (PBK), ribonucleotide reductase M2 (RRM2), and abnormal spindle homolog, and microcephaly-associated drosophila (ASPM) were the hub proteins with higher degrees in the PPI network. The cell cycle pathway (CDK1 enriched) and p53 signaling pathway (CDK1 and RRM2 enriched) were significantly enriched by DEGs.

CONCLUSION

CDK1, PBK, RRM2, and ASPM may be key genes for HCC transformation from cirrhosis. Furthermore, cell cycle and p53 signaling pathways may play vital mediatory roles; CDK1 may play crucial roles in HCC transformed from cirrhosis via cell cycle and p53 signaling pathways, and RRM2 might be involved in HCC transformed from cirrhosis via the p53 signaling pathway.

摘要

目的

我们旨在识别一些在肝硬化向肝细胞癌(HCC)转变过程中的关键基因和信号通路,并探索该疾病潜在的治疗靶点。

方法

从基因表达综合数据库下载GSE17548芯片数据,使用37个样本(20个肝硬化样本和17个HCC样本)进行分析。将HCC组织中的差异表达基因(DEGs)与肝硬化组织中的进行比较,并使用limma软件包进行分析。使用ClueGO和CluePedia工具包进行基因本体生物学过程和京都基因与基因组百科全书(KEGG)信号通路富集分析,并使用R软件包pathview分析关键KEGG信号通路。使用multiMiR R软件包从3个经过验证的miRNA靶标数据库中提取DEGs的调控因子miRNA。此外,使用Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络。

结果

在PPI网络中,包括细胞周期蛋白依赖性激酶1(CDK1)、PDZ结合激酶(PBK)、核糖核苷酸还原酶M2(RRM2)以及异常纺锤体同源物和小头畸形相关果蝇蛋白(ASPM)等DEGs是连接度较高的枢纽蛋白。细胞周期信号通路(富集CDK1)和p53信号通路(富集CDK1和RRM2)被DEGs显著富集。

结论

CDK1、PBK、RRM2和ASPM可能是肝硬化向HCC转变的关键基因。此外,细胞周期和p53信号通路可能发挥重要的介导作用;CDK1可能通过细胞周期和p53信号通路在肝硬化转变为HCC的过程中发挥关键作用,而RRM2可能通过p53信号通路参与肝硬化向HCC的转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08b0/5484182/b04494ae2273/medi-96-e6938-g001.jpg

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