School of Medicine, Shihezi University, Shihezi, China.
Department of Anaesthetic Operating Room, Provincial Otolaryngology Hospital Affiliated to Shandong University, Shandong Provincial Western Hospital, Jinan, China.
Oncol Res Treat. 2020;43(12):656-671. doi: 10.1159/000510534. Epub 2020 Oct 8.
Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis.
Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis.
GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.p value <0.05 and |logFC| ≥2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs.
A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out.
These discovered genes and small-molecule drugs provide some new ideas for further research on MPM.
恶性胸膜间皮瘤（MPM）与石棉暴露密切相关，是一种预后极差的极具侵袭性肿瘤。
本研究通过综合生物信息学分析，旨在阐明 MPM 的枢纽基因和潜在药物。
从基因表达综合数据库（GEO）中下载 GSE42977 数据集；采用 DAVID 数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析；采用 STRING 数据库构建蛋白质-蛋白质相互作用网络，采用 Cytoscape 进行模块分析和枢纽基因获取；采用基因表达谱分析交互分析（GEPIA）数据库评估枢纽基因对 MPM 患者预后的影响；采用药物-基因相互作用数据库（DGIdb）筛选相关药物。
共鉴定出 169 个上调和 70 个下调的差异表达基因（DEGs）。这些 DEGs 富集在细胞外基质-受体相互作用、黏着斑、PI3K-Akt 信号通路和 PPAR 信号通路等通路中。最后，鉴定出 10 个枢纽基因（CDC20、CDK1、UBE2C、TOP2A、CCNB2、NUSAP1、KIF20A、AURKA、CEP55 和 ASPM），这些基因被认为与 MPM 的不良预后密切相关。此外，还筛选出 119 种可能对 MPM 具有治疗作用的相关药物。
这些发现的基因和小分子药物为进一步研究 MPM 提供了一些新的思路。
