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Molecular mechanisms and therapeutic targets in glioblastoma multiforme: network and single-cell analyses

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作者：
Chen Xiangyu[1] * ; Zhong Xiao[1] * ; Zhang Feifei[2] ; Zhou Xiaomei[3] ; Yue Xiaofeng[4] ; Li Xueru[1] ;
机构： [1]Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Institute for Brain Science and Disease, Chongqing Medical University, Chongqing 400016, China. [2]Department of Blood Transfusion, School of Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610021, Sichuan, China. [3]Sichuan Provincial Chengdu Second People’s Hospital, Chengdu 610021, Sichuan, China. [4]Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
出处：
DOI： 10.1038/s41598-025-92867-z

关键词： Glioblastoma multiforme Weighted gene coexpression network analysis Single-cell RNA sequencing Molecular subtype Prognosis Tumor microenvironment Extracellular matrix

摘要：
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor associated with poor survival outcomes and is driven by a complex tumor microenvironment (TME) that promotes tumor progression and treatment resistance. To explore the role of the TME in GBM, we analyzed glioma-related microarray and single-cell RNA sequencing (scRNA-seq) datasets from the Gene Expression Omnibus (GEO). Functional enrichment and weighted gene coexpression network analyses revealed distinct immune profiles, metabolic alterations, and differences in chemotherapeutic drug sensitivity between the high-risk and low-risk patient groups. scRNA-seq data processed with the 'Seurat' package were used to identify differentially expressed genes in pericytes, endothelial cells, and glioma cells, particularly those involved in extracellular matrix (ECM) remodeling. A 17-gene prognostic signature developed through Cox regression and LASSO analyses revealed that key genes (COL1A1, COL4A1, and VIM) were significantly associated with survival outcomes in GBM patients. Drug sensitivity analyses using data from the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) identified potential targeted therapies for GBM, including SB-505,124, staurosporine, and AZD8186. This integrative study underscores the critical roles of the ECM and synaptic remodeling in GBM and suggests novel therapeutic targets to improve personalized treatment strategies for GBM patients.© 2025. The Author(s).

基金：
This research was supported by the National Natural Science Foundation of Chongqing Province (cstc2021j­cyj-bsh0238) and the Funding Project of The Third Affiliated Hospital of Chongqing Medical University (KY23054). Moreover, we wish to thank the curators of the databases, such as TCGA and GEO, which provided the data used for bioinformatics analyses.
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出版当年[2025]版：
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
最新[2025]版：
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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无
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

第一作者：
第一作者机构： [1]Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Institute for Brain Science and Disease, Chongqing Medical University, Chongqing 400016, China.
共同第一作者：
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推荐引用方式(GB/T 7714)：
Chen Xiangyu,Zhong Xiao,Zhang Feifei,et al.Molecular mechanisms and therapeutic targets in glioblastoma multiforme: network and single-cell analyses[J].Scientific Reports.2025,15(1):10558.doi:10.1038/s41598-025-92867-z.
APA：
Chen Xiangyu,Zhong Xiao,Zhang Feifei,Zhou Xiaomei,Yue Xiaofeng&Li Xueru.(2025).Molecular mechanisms and therapeutic targets in glioblastoma multiforme: network and single-cell analyses.Scientific Reports,15,(1)
MLA：
Chen Xiangyu,et al."Molecular mechanisms and therapeutic targets in glioblastoma multiforme: network and single-cell analyses".Scientific Reports 15..1(2025):10558

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