Association between plasma proteome and glioma: A two-sample Mendelian randomization analysis

Abstract

Purpose Glioma is the most common malignant tumor in the central nervous system, and patients generally have a poor prognosis. Biomarker research can help improve early diagnosis and treatment of gliomas. As plasma proteins can sample of the body's health status and is easy to access, it has become promising biomarkers for gliomas. Our objective is to explore the association between plasma proteins and glioma and to identify new therapeutic targets and biomarkers for glioma. Methods We used pQTLs of plasma proteins from the INTERVAL and Icelanders’ cohorts as instrumental variables and conducted Two-sample Mendelian randomization analyses using five models (Wald ratio, IVW, MR-Egger, Weighted Median, MRPRESSO). Results The results showed that 13 plasma proteins (CHST9, RACGAP1, IL18R1, FCRL3, ERAP1, GRN, MLN, TDGF1, SIRPB1, C1QTNF1, TAPBPL, TMPRSS11D, TPST2) had a causal relationship with gliomas, with five being risk factors (SIRPB1, RACGAP1, MLN, CHST9, TPST2) and eight being protective factors (TMPRSS11D, C1QTNF1, GRN, IL18R1, FCRL3, TAPBPL, ERAP1, TDGF1). Many of these are reported for the first time. Reverse Mendelian randomization analysis showed that there was no reverse causality between those proteins and glioma. Conclusion Our study reports multiple biomarkers for gliomas, which may provide some reference for the diagnosis and treatment of gliomas and future research.