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

Background

Glioblastoma multiforme (GBM) is the most frequent type of primary malignant brain tumor. This study utilized Mendelian randomization (MR) analysis to explore the causal link between proteins in plasma and cerebrospinal fluid and GBM.

Aims

This study aimed to identify proteins in both plasma and cerebrospinal fluid (CSF) that could serve as potential therapeutic targets for GBM.

Methods

We employed previously published protein quantitative trait loci (pQTL) data from CSF and plasma as the exposure data, alongside aggregated Genome-Wide Association Study (GWAS) data on GBM for our MR analysis. Furthermore, we conducted Bayesian co-localization analysis and examined the protein-protein interaction (PPI) networks of CSF and plasma proteins related to GBM risk.

Results

MR identified three key proteins linked to GBM risk: ribophorin I (RPN1) in plasma, von Willebrand factor (vWF) and macrophage-stimulating protein (MSP). in CSF. Elevated RPN1 and MSP were associated with decreased GBM risk, while increased vWF was linked to higher risk. External validation confirmed that RPN1 served as a key protein in GBM development. Bayesian co-localization showed a 10.35 % probability of a shared causal variant between RPN1 and GBM. Protein-protein interaction analysis further highlighted related proteins for RPN1.

Conclusions

In summary, the plasma protein RPN1 and the CSF proteins vWF and MSP are causally associated with the risk of GBM. Further research is needed to clarify the roles of these candidate proteins in GBM. Notably, RPN1 may serve as a potential therapeutic target for GBM. Future clinical studies on GBM treatment could explore drugs targeting RPN1.