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基于生物信息学分析的肝细胞癌预后标志物筛选枢纽基因。

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis.

机构信息

Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.

* Both the authors contributed equally to this article.

出版信息

Cell Transplant. 2019 Dec;28(1_suppl):76S-86S. doi: 10.1177/0963689719893950. Epub 2019 Dec 11.

Abstract

Hepatocellular carcinoma (HCC) is a widespread, common type of cancer in Asian countries, and the need for biomarker-matched molecularly targeted therapy for HCC has been increasingly recognized. However, the effective treatment for HCC is unclear. Therefore, identifying additional hub genes and pathways as novel prognostic biomarkers for HCC is necessary. In this study, the expression profiles of GSE121248, GSE45267 and GSE84402 were obtained from the Gene Expression Omnibus (GEO), including 132 HCC and 90 noncancerous liver tissues. Differentially expressed genes (DEGs) between HCC and noncancerous samples were identified by GEO2 R and Venn diagrams. In total, 109 DEGs were identified in these datasets, including 24 upregulated genes and 85 downregulated genes. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) preliminary analyses of the DEGs were performed using DAVID. The protein-protein interaction (PPI) network of the DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Module analysis of the PPI network was performed using MCODE to get hub genes. Moreover, the influence of the hub genes on overall survival was determined with Kaplan-Meier plotter. All hub genes were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and KEGG. Overall, the hub genes , , , , , , , , , , , , , , and were upregulated in HCC, and the survival rate was lower for HCC with increased expression of these hub genes. , , and were enriched in the p53 signaling pathway, and , , and were enriched in the cell cycle. In brief, we screened 15 hub genes and pathways to identify potential prognostic markers for HCC treatment. However, the specific occurrence and development of HCC with expression of the hub genes should be verified in vivo and .

摘要

肝细胞癌 (HCC) 是亚洲国家常见的广泛发生的癌症类型,越来越需要针对 HCC 的生物标志物匹配的分子靶向治疗。然而,HCC 的有效治疗方法尚不清楚。因此,有必要确定其他关键基因和途径作为 HCC 的新的预后生物标志物。在这项研究中,从基因表达综合数据库 (GEO) 中获得了 GSE121248、GSE45267 和 GSE84402 的表达谱,包括 132 例 HCC 和 90 例非癌性肝组织。使用 GEO2R 和 Venn 图鉴定 HCC 和非癌样本之间的差异表达基因 (DEG)。在这些数据集中共鉴定出 109 个 DEG,包括 24 个上调基因和 85 个下调基因。随后,使用 DAVID 对 DEG 进行基因本体论 (GO) 富集和京都基因与基因组百科全书 (KEGG) 初步分析。使用 Search Tool for the Retrieval of Interacting Genes (STRING) 构建 DEG 的蛋白质-蛋白质相互作用 (PPI) 网络,并在 Cytoscape 中可视化。使用 MCODE 对 PPI 网络进行模块分析以获取关键基因。此外,使用 Kaplan-Meier plotter 确定关键基因对总生存期的影响。使用基因表达谱分析交互分析 (GEPIA) 和 KEGG 对所有关键基因进行分析。总体而言,在 HCC 中上调了关键基因 、 、 、 、 、 、 、 、 、 、 、 和 ,并且这些关键基因表达增加的 HCC 的生存率较低。在 p53 信号通路中富集了 、 、 和 ,在细胞周期中富集了 、 、 和 。总之,我们筛选了 15 个关键基因和途径,以确定 HCC 治疗的潜在预后标志物。然而,应该在体内和 进一步验证表达这些关键基因的 HCC 的具体发生和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c083/7016461/00a5024f691b/10.1177_0963689719893950-fig1.jpg

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