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运用生物信息学分析鉴定非酒精性脂肪性肝病中的关键通路和基因

Identification of key pathways and genes in nonalcoholic fatty liver disease using bioinformatics analysis.

作者信息

Liu Jingqi, Lin Bogeng, Chen Zhiqing, Deng Manxiang, Wang Ye, Wang Jisu, Chen Luling, Zhang Zhenyu, Xiao Xueling, Chen Chunlin, Song Yang

机构信息

Department of Geriatrics, Zhongshan Hospital affiliated to Xiamen University, Xiamen, Fujian, China.

Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, Xiamen, Fujian, China.

出版信息

Arch Med Sci. 2020 Mar 2;16(2):374-385. doi: 10.5114/aoms.2020.93343. eCollection 2020.

Abstract

INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease in the world. However, the molecular mechanisms regulating the development of NAFLD have remained unclear.

MATERIAL AND METHODS

In the present study, we analyzed two public datasets (GSE48452 and GSE89632) to identify differentially expressed mRNAs in the progression of NAFLD. Next, we performed bioinformatics analysis to explore key pathways underlying NAFLD development.

RESULTS

Gene Ontology (GO) analysis showed that differentially expressed genes (DEGs) were mainly involved in regulating a series of metabolism-related pathways (including proteolysis and lipid metabolism), cell proliferation and adhesion, the inflammatory response, and the immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs in NAFLD were mainly enriched in the insulin signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and p53 signaling pathway. We also constructed protein-protein interaction (PPI) networks for these DEGs. Interestingly, we observed that key hub nodes in PPI networks were also associated with the progression of hepatocellular carcinoma (HCC).

CONCLUSIONS

Taken together, our analysis revealed that a series of pathways, such as metabolism and PPAR signaling pathways, were involved in NAFLD development. Moreover, we observed that many DEGs in NAFLD were also dysregulated in HCC. Although further validation is still needed, we believe this study could provide useful information to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets of NAFLD.

摘要

引言

非酒精性脂肪性肝病(NAFLD)是世界上最常见的肝病类型之一。然而,调节NAFLD发展的分子机制仍不清楚。

材料与方法

在本研究中,我们分析了两个公共数据集(GSE48452和GSE89632),以鉴定NAFLD进展过程中差异表达的mRNA。接下来,我们进行了生物信息学分析,以探索NAFLD发展的关键途径。

结果

基因本体论(GO)分析表明,差异表达基因(DEGs)主要参与调节一系列与代谢相关的途径(包括蛋白水解和脂质代谢)、细胞增殖和黏附、炎症反应以及免疫反应。京都基因与基因组百科全书(KEGG)途径分析表明,NAFLD中的DEGs主要富集于胰岛素信号通路、过氧化物酶体增殖物激活受体(PPAR)信号通路和p53信号通路。我们还构建了这些DEGs的蛋白质-蛋白质相互作用(PPI)网络。有趣的是,我们观察到PPI网络中的关键枢纽节点也与肝细胞癌(HCC)的进展有关。

结论

综上所述,我们的分析表明,一系列途径,如代谢和PPAR信号通路,参与了NAFLD的发展。此外,我们观察到NAFLD中的许多DEGs在HCC中也失调。尽管仍需要进一步验证,但我们相信这项研究可以为探索NAFLD的诊断、预后和药物靶点的潜在候选生物标志物提供有用的信息。

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