Investigating potential drug targets for the treatment of glioblastoma: a Mendelian randomization study
Hongwei Zhang1,2, Zixuan Wang1, Xiaolong Qiao1
1Department of Neurosurgery, Centre for Leading Medicine and Advanced Technologies of IHM, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Abstract:
Glioblastoma (GBM), one of the most aggressive brain tumors, has a 5-year survival rate of less than 5%. Current standard therapies, including surgery, radiotherapy, and temozolomide (TMZ) chemotherapy, are limited by drug resistance and the blood-brain barrier. Integrating expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data has shown promise in uncovering disease mechanisms and therapeutic targets. This study combined eQTL and pQTL analyses to identify potential GBM-related genes and circulating plasma proteins for therapeutic exploration. Using transcriptomic data from The Cancer Genome Atlas (TCGA), we identified 2,528 differentially expressed genes, including GPX7 and CXCL10. eQTL-MR analysis identifies GBM-associated differentially expressed genes and constructs a protein-protein interaction (PPI) network.Integrating pQTL data from the deCODE database, pQTL-MR, and colocalization analyses validated the therapeutic potential of GPX7 and CXCL10.These findings provide new perspectives on GBM biology and suggest actionable targets for therapy. Despite limitations due to sample size and population-specific data, this study highlights GPX7 and CXCL10 as promising candidates for further investigation and lays the foundation for targeted GBM treatments.
Insights
This study identifies GPX7 and CXCL10 as potential therapeutic targets for glioblastoma (GBM) by integrating genetic and proteomic data. These findings offer new avenues for developing more effective glioblastoma treatments.
Area of Science:
- Genomics
- Proteomics
- Oncology
- Neuroscience
Background:
- Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis.
- Current treatments face challenges due to drug resistance and the blood-brain barrier.
- Integrating expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data can reveal disease mechanisms and therapeutic targets.
Purpose of the Study:
- To identify novel GBM-related genes and circulating plasma proteins for therapeutic exploration.
- To leverage eQTL and pQTL data for uncovering GBM pathogenesis.
- To validate potential therapeutic targets for glioblastoma.
Main Methods:
- Analysis of transcriptomic data from The Cancer Genome Atlas (TCGA).
- eQTL-MR and pQTL-MR analyses to identify GBM-associated genes and proteins.
- Protein-protein interaction (PPI) network construction.
- Colocalization analyses using pQTL data from the deCODE database.
Main Results:
- Identified 2,528 differentially expressed genes in GBM, including GPX7 and CXCL10.
- Validated the therapeutic potential of GPX7 and CXCL10 through integrated genetic and proteomic analyses.
- Constructed a PPI network to understand gene interactions in GBM.
Conclusions:
- GPX7 and CXCL10 are promising candidates for targeted glioblastoma therapy.
- This study provides new insights into GBM biology and potential therapeutic strategies.
- The findings lay the groundwork for future clinical investigations into novel GBM treatments.
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