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利用 WGCNA 对多形性胶质母细胞瘤的候选生物标志物和分子机制进行研究。

Candidate Biomarkers and Molecular Mechanism Investigation for Glioblastoma Multiforme Utilizing WGCNA.

机构信息

Department of Gynecology and Obstetrics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.

Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.

出版信息

Biomed Res Int. 2018 Sep 26;2018:4246703. doi: 10.1155/2018/4246703. eCollection 2018.

Abstract

To reveal the potential molecular mechanism of glioblastoma multiforme (GBM) and provide the candidate biomarkers for GBM gene therapy. Microarray dataset GSE50161 was obtained from GEO database. The differentially expressed genes (DEGs) were identified between GBM samples and control samples, followed by the module partition analysis based on WGCNA. Then, the pathway and functional enrichment analyses of DEGs were performed. The hub genes were further investigated, followed by the survival analysis and data validation. A total of 1913 DEGs were investigated between two groups, followed by analysis of 5 modules using WGCNA. These DEGs were mainly enriched in functions like inflammatory response. The hub genes including upregulated N-Myc and STAT Interactor (NMI), Capping Actin Protein-Gelsolin Like (CAPG), and Proteasome Subunit Beta 8 (PSMB8) were revealed as potential liquid biopsy molecules for GBM diagnose. Moreover, Nucleolar and Spindle Associated Protein 1 (NUSAP1) and G Protein-Coupled Receptor 65 (GPR65) were outstanding genes in survival analysis. Our results suggested that CPNE6, HAPLN2, CMTM3, NMI, CAPG, and PSMB8 might be used as potential molecules for liquid biopsy of GBM. NUSAP1 and GPR65 might be novel prognostic targets for GBM gene therapy. Furthermore, the upregulated NMI might play an important role in GBM progression via inflammatory response.

摘要

为了揭示胶质母细胞瘤(GBM)的潜在分子机制,并为 GBM 的基因治疗提供候选生物标志物。从 GEO 数据库中获取了微阵列数据集 GSE50161。在 GBM 样本和对照样本之间鉴定了差异表达基因(DEGs),然后基于 WGCNA 进行了模块划分分析。然后,对 DEGs 进行了通路和功能富集分析。进一步研究了枢纽基因,随后进行了生存分析和数据验证。在两组之间共研究了 1913 个 DEGs,然后使用 WGCNA 分析了 5 个模块。这些 DEGs 主要富集在炎症反应等功能中。上调的 N-Myc 和 STAT 相互作用物(NMI)、肌动蛋白封端蛋白-凝胶蛋白样(CAPG)和蛋白酶体亚基β 8(PSMB8)等枢纽基因被揭示为 GBM 诊断的潜在液体活检分子。此外,核仁纺锤体相关蛋白 1(NUSAP1)和 G 蛋白偶联受体 65(GPR65)在生存分析中是突出的基因。我们的结果表明,CPNE6、HAPLN2、CMTM3、NMI、CAPG 和 PSMB8 可能被用作 GBM 液体活检的潜在分子。NUSAP1 和 GPR65 可能是 GBM 基因治疗的新的预后靶标。此外,上调的 NMI 可能通过炎症反应在 GBM 进展中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcd2/6178162/bad571a8045e/BMRI2018-4246703.001.jpg

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