Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy
IntroductionGlioblastoma (GBM) is a highly aggressive brain tumor characterized by pronounced invasiveness, rapid progression, frequent recurrence, and poor clinical prognosis. Current treatment strategies remain inadequate due to the lack of effective molecular targets, underscoring the urgent need...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610683/full |
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| author | Zhaoming Song Fei Wang Chen Yang Yanao Guo Jinfeng Li Run Huang Hongyi Ling Guosheng Cheng Zhouqing Chen Zhanchi Zhu Zhong Wang |
| author_facet | Zhaoming Song Fei Wang Chen Yang Yanao Guo Jinfeng Li Run Huang Hongyi Ling Guosheng Cheng Zhouqing Chen Zhanchi Zhu Zhong Wang |
| author_sort | Zhaoming Song |
| collection | DOAJ |
| description | IntroductionGlioblastoma (GBM) is a highly aggressive brain tumor characterized by pronounced invasiveness, rapid progression, frequent recurrence, and poor clinical prognosis. Current treatment strategies remain inadequate due to the lack of effective molecular targets, underscoring the urgent need to identify novel therapeutic avenues.MethodsIn this study, we employed weighted gene co-expression network analysis and meta-analysis, incorporating clinical immunotherapy datasets, to identify ten candidate genes associated with GBM initiation, progression, prognosis, and response to immunotherapy. Multi-omics analyses across glioma and pan-cancer datasets revealed that these genes play pivotal roles in cancer biology.ResultsPhospholipase Cb4 (PLCB4) showed a negative correlation with tumor grade in clinical samples, suggesting its potential role as a tumor suppressor. Evidence indicated that PLCB4 expression is modulated by Wnt signaling, and its overexpression may activate the calcium ion signaling pathway. Notably, PLCB4 is strongly associated with aberrant tumor proliferation, making it a compelling therapeutic target. Through structure-based virtual screening, five small molecules with high predicted affinity for PLCB4 were identified as potential drug candidates.DiscussionThis study’s integrative approach—combining target identification, pathway inference, and in silico drug screening—offers a promising framework for rational drug development in GBM. The findings may reduce unnecessary experimental screening and medical costs, and represent a significant step toward improving therapeutic outcomes and prognosis for GBM patients. |
| format | Article |
| id | doaj-art-c7e0077d4b1c467287c247acf6233299 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c7e0077d4b1c467287c247acf62332992025-08-20T03:40:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16106831610683Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapyZhaoming Song0Fei Wang1Chen Yang2Yanao Guo3Jinfeng Li4Run Huang5Hongyi Ling6Guosheng Cheng7Zhouqing Chen8Zhanchi Zhu9Zhong Wang10Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaSuzhou Medical College of Soochow University, Suzhou, Jiangsu, ChinaSuzhou Medical College of Soochow University, Suzhou, Jiangsu, ChinaSuzhou Medical College of Soochow University, Suzhou, Jiangsu, ChinaSuzhou Medical College of Soochow University, Suzhou, Jiangsu, ChinaChinese Academy of Sciences (CAS) Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaChinese Academy of Sciences (CAS) Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaIntroductionGlioblastoma (GBM) is a highly aggressive brain tumor characterized by pronounced invasiveness, rapid progression, frequent recurrence, and poor clinical prognosis. Current treatment strategies remain inadequate due to the lack of effective molecular targets, underscoring the urgent need to identify novel therapeutic avenues.MethodsIn this study, we employed weighted gene co-expression network analysis and meta-analysis, incorporating clinical immunotherapy datasets, to identify ten candidate genes associated with GBM initiation, progression, prognosis, and response to immunotherapy. Multi-omics analyses across glioma and pan-cancer datasets revealed that these genes play pivotal roles in cancer biology.ResultsPhospholipase Cb4 (PLCB4) showed a negative correlation with tumor grade in clinical samples, suggesting its potential role as a tumor suppressor. Evidence indicated that PLCB4 expression is modulated by Wnt signaling, and its overexpression may activate the calcium ion signaling pathway. Notably, PLCB4 is strongly associated with aberrant tumor proliferation, making it a compelling therapeutic target. Through structure-based virtual screening, five small molecules with high predicted affinity for PLCB4 were identified as potential drug candidates.DiscussionThis study’s integrative approach—combining target identification, pathway inference, and in silico drug screening—offers a promising framework for rational drug development in GBM. The findings may reduce unnecessary experimental screening and medical costs, and represent a significant step toward improving therapeutic outcomes and prognosis for GBM patients.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610683/fullglioblastomaPLCB4machine learningtumor microenvironmentmulti-omicsimmunotherapy |
| spellingShingle | Zhaoming Song Fei Wang Chen Yang Yanao Guo Jinfeng Li Run Huang Hongyi Ling Guosheng Cheng Zhouqing Chen Zhanchi Zhu Zhong Wang Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy Frontiers in Immunology glioblastoma PLCB4 machine learning tumor microenvironment multi-omics immunotherapy |
| title | Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy |
| title_full | Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy |
| title_fullStr | Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy |
| title_full_unstemmed | Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy |
| title_short | Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²+ signaling mediator in glioblastoma immunotherapy |
| title_sort | meta analysis of multi center transcriptomic profiles and machine learning reveal phospholipase cβ4 as a wnt ca² signaling mediator in glioblastoma immunotherapy |
| topic | glioblastoma PLCB4 machine learning tumor microenvironment multi-omics immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610683/full |
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