Research Paper Volume 15, Issue 19 pp 10146—10167

GPR37 expression as a prognostic marker in gliomas: a bioinformatics-based analysis

Kairong Liang1, *, , Zhaoxiong Guo2, *, , Shizhen Zhang1, *, , Danmin Chen1, , Renheng Zou1, , Yuhao Weng1, , Chengxiang Peng1, , Zhichao Xu1, , Jingbai Zhang1, , Xiaorui Liu4, , Xiao Pang1, , Yunxiang Ji1, , Degui Liao1, , Miaoling Lai1, , Huaidong Peng3, , Yanbin Ke1, , Zhaotao Wang1, , Yezhong Wang1, ,

  • 1 Institute of Neuroscience, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
  • 2 Science and Technology Innovation Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
  • 3 Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
  • 4 Department of Pharmacy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
* Equal contribution

Received: April 18, 2023       Accepted: August 21, 2023       Published: October 13, 2023
How to Cite

Copyright: © 2023 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Gliomas are the most frequently diagnosed primary brain tumors, and are associated with multiple molecular aberrations during their development and progression. GPR37 is an orphan G protein-coupled receptor (GPCR) that is implicated in different physiological pathways in the brain, and has been linked to various malignancies. The aim of this study was to explore the relationship between GPR37 gene expression and the clinicopathological factors, patient prognosis, tumor-infiltrating immune cell signature GSEA and methylation levels in glioma.

Methods: We explored the diagnostic value, clinical relevance, and molecular function of GPR37 in glioma using TCGA, STRING, cBioPortal, Tumor Immunity Estimation Resource (TIMER) database and MethSurv databases. Besides, the "ssGSEA" algorithm was conducted to estimate immune cells infiltration abundance, with 'ggplot2' package visualizing the results. Immunohistochemical staining of clinical samples were used to verify the speculations of bioinformatics analysis.

Results: GPR37 expression was significantly higher in the glioma tissues compared to the normal brain tissues, and was linked to poor prognosis. Functional annotation of GPR37 showed enrichment of ether lipid metabolism, fat digestion and absorption, and histidine metabolism. In addition, GSEA showed that GPR37 was positively correlated to the positive regulation of macrophage derived foam cell differentiation, negative regulation of T cell receptor signaling pathway, neuroactive ligand receptor interaction, calcium signaling pathway, and negatively associated with immunoglobulin complex, immunoglobulin complex circulating, ribosome and spliceosome mediated by circulating immunoglobulin etc. TIMER2.0 and ssGSEA showed that GPR37 expression was significantly associated with the infiltration of T cells, CD8 T cell, eosinophils, macrophages, neutrophils, NK CD56dim cells, NK cells, plasmacytoid DCs (pDCs), T helper cells and T effector memory (Tem) cells. In addition, high GPR37 expression was positively correlated with increased infiltration of M2 macrophages, which in turn was associated with poor prognosis. Furthermore, GPR37 was positively correlated with various immune checkpoints (ICPs). Finally, hypomethylation of the GPR37 promoter was associated with its high expression levels and poor prognosis in glioma.

Conclusion: GPR37 had diagnostic and prognostic value in glioma. The possible biological mechanisms of GPR37 provide novel insights into the clinical diagnosis and treatment of glioma.


aDCs: activated DCs; BBB: blood-brain barrier; CNS: central nervous system; DSS: disease-specific survival; GBM: glioblastoma; GPR37: G Protein-Coupled Receptor 37; GPCRs: G-protein-coupled receptors; GO: Gene Ontology; ICPs: immune checkpoints; ICIs: immune checkpoint inhibitors; iDCs: immature DCs; IHC: immunohistochemistry; KEGG: Kyoto Encyclopedia of Genes and Genomes; LGG: low-grade gliomas; OS: overall survival; pDCs: plasmacytoid DCs; ssGSEA: single-sample Gene Set Enrichment Analysis; TAMs: Tumor associated macrophages; TCGA: The Cancer Genome Atlas; Tcm: T central memory cells; Tem: T effector memory cells; Tfh: T follicular helper cells; Tgd: T gamma delta cells.