Low expression of GRM4 is associated with poor prognosis and tumor immune infiltration in glioma.

Int J Neurosci

Engineering Research Center of Tropical Medicine Innovation and Transformation, Ministry of Education, Hainan Medical University, Haikou, China.

Published: December 2024

AI Article Synopsis

  • The study investigates the role of metabotropic glutamate receptor 4 (mGlu4) in glioma, finding that lower expression levels are linked to worse patient outcomes.
  • Utilizing RNA-sequencing data from multiple cancer databases, researchers identified key factors like DNA methylation and specific microRNAs that regulate GRM4 expression.
  • Results indicate that reduced GRM4 expression correlates with shorter overall survival, highlighting its potential as a prognostic biomarker for glioma patients.

Article Abstract

Introduction: The metabotropic glutamate receptor 4 (mGlu4, GRM4) exhibits significant expression within the central nervous system (CNS) and has been implicated to be correlated with a poor prognosis.

Objective: This study was aimed to elucidate the relationship between the expression profile of GRM4 and the prognosis of glioma patients.

Methods: RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and China Glioma Genome Atlas (CGGA) repositories were used to evaluate the potential relationship. The value of clinical prognostic about GRM4 was assessed using clinical survival data from CGGA and TCGA. The GEPIA database was used to select genes like GRM4. PPI network was constructed by the database of (STRING), GO and KEGG analyses were performed. TargetScan, TarBase, miRDB, and starBase were used to explore miRNAs that could regulate GRM4 expression. EWAS Data Hub, MethSurv, and MEXPRESS were used for the analysis and relationship between DNA methylation and GRM4 expression and prognosis in glioma. TIMER2.0 and CAMOIP databases were used to assess the association between immune cell infiltration and GRM4. Human GBM cell lines were used to validate the function of GRM4.

Results: Our study shows that GRM4 is under expressed among gliomas and accompanied by poorer OS. Multivariate analysis showed that low mRNA expression of GRM4 was an independent factor of prognostic for shorter OS in all glioma patients. MiR-1262 affects the malignant phenotype of gliomas through GRM4. Methylation of DNA plays an important role in the instruction of GRM4 expression, the methylation level of GRM4 in glioma tissue is higher in comparison to normal tissue, and the higher methylation level was accompanied with the worse prognosis. Further analysis showed that mRNA expression in GBM linked negatively with common lymphoid progenitor, Macrophage M1, Macrophage, and T cell CD4 Th2, but not with the tumor purity. Overexpression of GRM4 prevents the migration of human GBM cell lines in vitro.

Conclusion: GRM4 may have a substantial impact on the infiltration of immune cells and serve as a valuable prognostic biomarker in gliomas.

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Source
http://dx.doi.org/10.1080/00207454.2023.2297646DOI Listing

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