Deciphering Glioblastoma Pathogenesis: Insights from Mitophagy Dysregulation and SNX7 as a Therapeutic Target

Brain Res Bull. 2024 Dec 28:111184. doi: 10.1016/j.brainresbull.2024.111184. Online ahead of print.

Abstract

Background: Glioblastoma is a highly aggressive and invasive brain tumor with an extremely poor prognosis. The aims of the present study are to investigate the pathogenesis of glioblastoma and identify potential therapeutic targets.

Methods: We performed a systematic analysis of gene expression data from multiple datasets, including GEO and TCGA, to identify hub genes and pathways associated with glioblastoma progression. Bioinformatics tools were utilized to analyze differential gene expression, pathway enrichment and survival prognosis. Both in vitro and in vivo functional experiments were conducted to validate biological roles of SNX7.

Results: Pathway analysis revealed significant enrichment of the mitophagy pathway in glioblastoma, indicating its critical role in tumor development. We identified 12 hub genes associated with glioblastoma prognosis, with high-risk patients having worse survival outcomes. Among the hub gene set, sorting nexin 7 (SNX7) was found to be the most significant regulator of glioblastoma progression. Our results also demonstrated that SNX7 expression is associated with tumor ferroptosis and genomic variations, representing potential biomarkers for clinical diagnosis and treatment. Furthermore, functional experiments confirmed that SNX7 promotes glioblastoma cell proliferation, invasion and survival by inhibiting protective mitophagy.

Conclusion: Our results highlight the importance of mitophagy dysregulation in the pathogenesis of glioblastoma and identify SNX7 as a novel therapeutic target. Further research is needed to elucidate the underlying mechanisms of SNX7 in glioblastoma and validate its clinical significance. These findings may facilitate the development of personalized treatment strategies and improve outcomes for glioblastoma patients.

Keywords: Autophagy; Gene expression profiling; Glioblastoma; Mitophagy prognostic model; Sorting Nexin 7.