A multi-omics target study for glioblastoma multiforme (GBM) based on Mendelian randomization analysis

Area of Science:

• Neuro-oncology
• Genetics
• Biomarker Discovery

Background:

• Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor.
• Identifying reliable biomarkers and therapeutic targets for GBM remains a critical challenge.
• This study investigates potential causal relationships between circulating and cerebrospinal fluid proteins and GBM risk.

Purpose of the Study:

• To identify proteins in plasma and cerebrospinal fluid (CSF) causally associated with GBM risk.
• To explore potential therapeutic targets for GBM based on identified protein associations.
• To investigate the functional relationships of candidate GBM-associated proteins.

Main Methods:

• Mendelian randomization (MR) analysis using protein quantitative trait loci (pQTL) and GBM Genome-Wide Association Study (GWAS) data.
• Bayesian co-localization analysis to assess shared causal variants.
• Protein-protein interaction (PPI) network analysis to explore functional relationships.

Main Results:

• MR analysis identified three proteins causally linked to GBM: plasma ribophorin I (RPN1), and CSF von Willebrand factor (vWF) and macrophage-stimulating protein (MSP).
• Elevated RPN1 and MSP were associated with decreased GBM risk, while increased vWF correlated with higher GBM risk.
• RPN1 was validated as a key protein in GBM development, with a 10.35% probability of a shared causal variant with GBM.

Conclusions:

• Plasma RPN1 and CSF vWF and MSP are causally associated with GBM risk.
• RPN1 emerges as a potential therapeutic target for GBM treatment.
• Further research is warranted to elucidate the precise roles of these proteins in GBM pathogenesis and to explore clinical applications.