AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025140076
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ORIGINAL RESEARCH ARTICLE

Targeting STAT3 enhances glioblastoma therapeutic sensitivity through valproic acid-mediated regulation of the tumor microenvironment

Leina Li1 ,  Moli Wu1 ,  Xu Zheng1 ,  Jia Liu1*
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1 Liaoning Laboratory of Cancer Genomics and Epigenomics, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
EJMO, 025140076 https://doi.org/10.36922/EJMO025140076
Received: 31 March 2025 | Revised: 29 April 2025 | Accepted: 9 May 2025 | Published online: 23 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Glioblastoma (GBM) is a highly malignant tumor of the nervous system, posing serious threats to patient survival and quality of life. However, current treatment options remain limited in both availability and effectiveness. Objective: This study analyzes the gene expression data related to GBM to support the development of improved therapeutic strategies. Methods: Two gene expression datasets were selected for statistical analysis. Differentially expressed genes (DEGs) related to GBM were screened based on predefined criteria. Enrichment analysis was performed to explore the biological processes and pathways involved. A protein-protein interaction (PPI) network was constructed to identify central genes, which were further analyzed for expression patterns and their potential roles in GBM pathology. Results: A total of 1,151 overlapping DEGs were identified. Enrichment analysis revealed their involvement in several key biological processes and pathways. From the PPI network, central genes, including signal transducer and activator of transcription 3 (STAT3), CAML1, clathrin assembly lymphoid myeloid 2, and protein kinase CAMP-activated catalytic subunit beta were identified as playing crucial roles in GBM development. Immune cell subtype analysis indicated interactions between these genes and the tumor microenvironment. The diagnostic value highlighted STAT3 as a potential biomarker for GBM. In vivo experiments confirmed that gene expression patterns were consistent with database predictions. Molecular docking analysis identified valproic acid as a promising therapeutic candidate, targeting five central genes. In vitro studies demonstrated that valproic acid effectively induced GBM cell death and modulated the expression of these genes, with high safety observed. Conclusion: Identifying DEGs and central genes is essential in understanding GBM pathology. This study establishes STAT3 as a diagnostic marker and highlights valproic acid as a potential multi-target therapeutic agent. These findings lay the groundwork for more effective and targeted treatment strategies for GBM.

Keywords
Glioblastoma
Signal transducer and activator of transcription 3
Differentially expressed genes
Valproic acid
Funding
None.
Conflict of interest
The authors declare no conflicts of interest.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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