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Integrative multi-omics analysis reveals BEST1 as a potential tumor-associated gene in gliomas
Zili Qiu1, Chengcheng Guo2, Xuejiao Liu1
1Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, China.
Background:
The newest glioma classification in WHO 2021 emphasizes the importance of gene mutations in the glioma molecular pathogenesis. Our research aims to look for new glioma-related genes that have the potential to be therapeutic targets.
Methods:
We applied Mendelian randomization and colocalization analysis to identify the target genes. Artificial intelligence-based methods were employed to evaluate the prognostic significance of the target gene in patient outcomes. Bioinformatics was then utilized to explore the expression and function of the gene in gliomas. Finally, we found the gene targeted drugs by Drug Signatures Database which is primarily used to explore the effects of drugs on gene expression and drug repurposing, and carried out molecular docking to evaluate the interaction between gene and drugs.
Results:
Bestrophin-1 (BEST1) is the only gene that passes the MR and colocalization analysis. Bioinformatics analyses demonstrated that BEST1 showed significant associations in glioma. We identified chlorothiazide as a therapeutic target drug associated with BEST1, which has not been previously studied in gliomas.
Conclusion:
Our findings validate BEST1 as a potential therapeutic target for gliomas through various approaches. We predicted chlorothiazide as a fresh candidate for glioma treatment and provided a new direction for the research in the future.
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