Identifying Hub Genes and MicroRNAs as Potential Biomarkers for Pediatric Glioblastoma: A Bioinformatics Analysis

Glioblastoma is a primary brain tumor characterized by its aggressive nature and resistance to conventional therapies. When it arises in children, it presents a particularly formidable challenge due to the unique biological features of pediatric tumors. Gene expression data analysis using bioinformatics tolls can help identify potential biomarkers. This study aimed to investigate the molecular mechanisms underlying glioblastoma to identify hub genes as glioblastoma biomarkers in pediatrics by analyzing differentially expressed genes (DEGs). Methods: The GSE۲۴۳۶۸۲ dataset was acquired consisting of ۱۷ glioblastoma and ۵ normal samples. Differentially expressed genes (DEGs) were identifies using criteria of |log۲FC|>۳ and P-values<۰.۰۱. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were served by Enricher. Protein-protein interaction (PPI) network generated from STRING database and visualized via Cytoscape. Hub genes were defined using degree method in Cytoscape’s cytoHubba plug-in, and interaction network for microRNA (miRNA)-hub genes were evaluated by using miRDB. Additionally, GEPIA۲ database was utilized to conduct survival analysis. Result: A total of ۷۴۰ differentially expressed genes (DEGs) were identified, comprising ۳۰۱ upregulated and ۴۳۹ downregulated genes. KEGG analysis revealed that upregulated DEGs were predominantly involved in ribosome biogenesis, whereas downregulated DEGs were enriched in neuroactive ligand-receptor interaction. Hub genes were identified based on the top ۱۰ genes with the highest degree in the protein-protein interaction (PPI) network: IL۶ (downregulated), TNF (upregulated), SNAP۲۵ (downregulated), SLC۳۲A۱ (downregulated), ESR۱ (upregulated), SLC۱۷A۷ (downregulated), SLC۱۷A۶ (downregulated), POMC (downregulated), DRD۲ (downregulated), and CAMK۲A (downregulated). We identified miRNAs associated with these hub genes, including hsa-miR-۱۱۱۸۱-۵p for IL۶, hsa-miR-۵۶۹۲a for TNF, hsa-miR-۶۸۶۷-۵p for SNAP۲۵, hsa-miR-۳۹۱۴ for SLC۳۲A۱, hsa-miR-۱۹a-۳p for ESR۱, hsa-miR-۴۷۳۸-۳p for SLC۱۷A۷, hsa-let-۷f-۲-۳p for SLC۱۷A۶, hsa-miR-۴۷۶۴-۵p for POMC, hsa-miR-۳۲۰۲ for DRD۲, and hsa-miR-۴۷۹۵-۳p for CAMK۲A. However, survival analysis indicated that none of these genes were significantly associated with overall survival. Conclusion: This research identified five key genes—IL۶, TNF, SNAP۲۵, SLC۳۲A۱, ESR۱, SLC۱۷A۷, SLC۱۷A۶, POMC, DRD۲, and CAMK۲A—as potential biomarkers for pediatric glioblastoma. These findings could offer valuable insights into diagnosing, predicting outcomes, and developing effective treatments for this type of cancer. However, additional studies are necessary to verify the significance of these genes and the underlying biological processes involved.

کلیدواژه ها:

Glioblastoma ، Pediatrcics ، Biomarkers ، miRNA ، Hub gene