Exploring the relationship between MGAT2 and glioblastoma: A Mendelian Randomization and bioinformatics approach

Zili Qiu; Chengcheng Guo; Xuejiao Liu; Shangfeng Gao; Weihan Xiao; Hai Cheng; Luxin Yin

doi:10.1016/j.brainres.2025.149449

Exploring the relationship between MGAT2 and glioblastoma: A Mendelian Randomization and bioinformatics approach

Brain Res. 2025 Jan 7:149449. doi: 10.1016/j.brainres.2025.149449. Online ahead of print.

Authors

Zili Qiu¹, Chengcheng Guo², Xuejiao Liu¹, Shangfeng Gao¹, Weihan Xiao¹, Hai Cheng¹, Luxin Yin³

Affiliations

¹ Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, China.
² Department of Intensive Care Unit, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
³ Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, China. Electronic address: yinluxin530@163.com.

PMID: 39788365
DOI: 10.1016/j.brainres.2025.149449

Abstract

Background: Mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase 2 (MGAT2) and tumors' relevant research was in full swing recently. Therefore, we employed Mendelian Randomization (MR) alongside bioinformatics to thoroughly investigate the possible relationship between MGAT2 and glioblastoma (GBM).

Methods: We utilized the summary statistics of genome-wide association studies (GWAS) for MGAT2 (N = 35,559 from deCODE) and glioblastoma (N = 379,155 from FinnGen). MR was used to assess the causal relationship between MGAT2 and GBM. Bioinformatics was used for a more in-depth exploration of the relationship between MGAT2 and GBM.

Results: MR analysis demonstrated a causal relationship, showing that elevated levels of MGAT2 are associated with an increased risk of GBM (OR = 2.59, 95 % CI: 1.13-5.91, p = 0.023). Further investigation revealed significant differences in MGAT2 expression across normal tissue, tumor tissue, and gliomas of different types. Additionally, we found that MGAT2 may influence GBM through immune-related pathways, particularly through the role of macrophages. Proteins associated with MGAT2 were also identified in the PPI network.

Conclusion: This study first validated the causal relationship between MGAT2 and glioblastoma, and used bioinformatics to explore the relationship from multiple perspectives. Additionally, we proposed hypotheses for further research to investigate the potential mechanisms underlying this connection.

Keywords: Bioinformatics; Glioblastoma; MGAT2; Mendelian Randomization.