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[乙型肝炎病毒相关肝细胞癌核心差异表达基因的生物信息学分析]

[Bioinformatics analysis of core differentially expressed genes in hepatitis B virus-related hepatocellular carcinoma].

作者信息

Yu Y, Cheng J, Mei C Z, Dai Y Z

机构信息

School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233000, China.

Department of Clinical Research, The 903rd Hospital of Joint Logistics Support Forces of Chinese People 's Liberation Army, Hangzhou, Zhejiang 310013, China.

出版信息

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2022 Nov 21;34(5):507-513. doi: 10.16250/j.32.1374.2021292.

Abstract

OBJECTIVE

To identify the core genes associated with the development and progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), so as to provide insights into the elucidation of pathogenesis of HBV-related HCC.

METHODS

GSE55092 and GSE121248 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between HCC and peri-cancer tissues were screened using the R package, and the volcano map of DEGs were plotted. The DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and a protein-protein interaction (PPI) network was created. The hub DEGs were screened using Molecular Complex Detection (MCODE) and cytoHubba plugins in the open-access platform Cytoscape 3.9.0. Then, the screened hub DEGs were validated for differential expression and survival analysis using clinical sample data captured from the UALCAN and Kaplan Meier-plotter databases.

RESULTS

A total of 1 148 and 686 DEGs were screened between HCC and peri-cancer tissues in GSE55092 and GSE121248 datasets, including 703 and 477 down-regulated genes and 445 and 209 up-regulated genes, respectively. A total of 557 common DEGs were screened between GSE55092 and GSE121248 datasets, including 384 down-regulated genes and 173 up-regulated genes. GO enrichment analysis showed that these DEGs were significantly enriched in biological processes of cell division, cell proliferation, redox process, immune response and proteolysis, cellular components of cell nucleus, cytoplasm, extracellular vesicle and endoplasmic reticulum membrane, and molecular functions of binding to calcium ion, protein kinase, DNA and heme. KEGG pathway analysis revealed that these DEGs were significantly enriched in pathways of cell cycle, oocyte meiosis, metabolic pathway, antibiotic biosynthesis and p53 signaling. PPI network analysis identified 10 DEGs, including , , , , , , , , and , and , and were found to be differentially expressed and correlate with poor prognosis among HBV-related HCC patients following clinical sample data validation.

CONCLUSIONS

, and may play a critical role in the development and progression of HBV-related HCC, which may be potential diagnostic biomarkers and therapeutic targets of HBV-related HCC.

摘要

目的

鉴定与乙型肝炎病毒(HBV)相关肝细胞癌(HCC)发生发展相关的核心基因,为阐明HBV相关HCC的发病机制提供思路。

方法

从基因表达综合数据库(GEO)下载GSE55092和GSE121248数据集。使用R包筛选HCC与癌旁组织之间的差异表达基因(DEG),并绘制DEG的火山图。对DEG进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,并构建蛋白质-蛋白质相互作用(PPI)网络。使用开放获取平台Cytoscape 3.9.0中的分子复合物检测(MCODE)和cytoHubba插件筛选枢纽DEG。然后,使用从UALCAN和Kaplan Meier-plotter数据库获取的临床样本数据对筛选出的枢纽DEG进行差异表达验证和生存分析。

结果

在GSE55092和GSE121248数据集中,分别在HCC与癌旁组织之间筛选出1148个和个686 DEG,其中下调基因分别为703个和477个,上调基因分别为445个和209个。在GSE55092和GSE121248数据集之间共筛选出557个共同DEG,其中下调基因384个,上调基因173个。GO富集分析表明,这些DEG在细胞分裂、细胞增殖、氧化还原过程、免疫反应和蛋白水解等生物学过程,细胞核、细胞质、细胞外囊泡和内质网膜等细胞成分,以及与钙离子、蛋白激酶、DNA和血红素结合的分子功能方面显著富集。KEGG通路分析显示,这些DEG在细胞周期途径、卵母细胞减数分裂、代谢途径、抗生素生物合成和p53信号通路中显著富集。PPI网络分析确定了10个DEG,包括……,经临床样本数据验证,发现……在HBV相关HCC患者中差异表达且与预后不良相关。

结论

……可能在HBV相关HCC的发生发展中起关键作用,可能是HBV相关HCC潜在的诊断生物标志物和治疗靶点。

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