Institute of Neuroscience, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
Science and Technology Innovation Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Aging (Albany NY). 2023 Oct 13;15(19):10146-10167. doi: 10.18632/aging.205063.
Gliomas are the most frequently diagnosed primary brain tumors, and are associated with multiple molecular aberrations during their development and progression. 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 gene expression and the clinicopathological factors, patient prognosis, tumor-infiltrating immune cell signature GSEA and methylation levels in glioma.
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.
expression was significantly higher in the glioma tissues compared to the normal brain tissues, and was linked to poor prognosis. Functional annotation of showed enrichment of ether lipid metabolism, fat digestion and absorption, and histidine metabolism. In addition, GSEA showed that 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 expression was significantly associated with the infiltration of T cells, CD8 T cell, eosinophils, macrophages, neutrophils, NK CD56 cells, NK cells, plasmacytoid DCs (pDCs), T helper cells and T effector memory (Tem) cells. In addition, high expression was positively correlated with increased infiltration of M2 macrophages, which in turn was associated with poor prognosis. Furthermore, was positively correlated with various immune checkpoints (ICPs). Finally, hypomethylation of the promoter was associated with its high expression levels and poor prognosis in glioma.
had diagnostic and prognostic value in glioma. The possible biological mechanisms of provide novel insights into the clinical diagnosis and treatment of glioma.
神经胶质瘤是最常见的原发性脑肿瘤,其在发生和发展过程中存在多种分子异常。GPR37 是一种孤儿 G 蛋白偶联受体(GPCR),它参与大脑中的不同生理途径,并与多种恶性肿瘤有关。本研究旨在探讨 GPR37 基因表达与神经胶质瘤临床病理因素、患者预后、肿瘤浸润免疫细胞特征 GSEA 和甲基化水平的关系。
我们使用 TCGA、STRING、cBioPortal、肿瘤免疫评估资源(TIMER)数据库和 MethSurv 数据库探讨了 GPR37 在神经胶质瘤中的诊断价值、临床相关性和分子功能。此外,我们使用'ssGSEA'算法估计免疫细胞浸润丰度,并使用'ggplot2'包可视化结果。使用临床样本的免疫组织化学染色来验证生物信息学分析的推测。
与正常脑组织相比,神经胶质瘤组织中表达明显升高,与预后不良相关。GPR37 的功能注释显示醚脂质代谢、脂肪消化和吸收以及组氨酸代谢的富集。此外,GSEA 显示 GPR37 与巨噬细胞衍生泡沫细胞分化的正调控、T 细胞受体信号通路的负调控、神经活性配体受体相互作用、钙信号通路以及免疫球蛋白复合物、免疫球蛋白复合物循环、核糖体和剪接体介导的循环免疫球蛋白等呈正相关。TIMER2.0 和 ssGSEA 显示 GPR37 表达与 T 细胞、CD8 T 细胞、嗜酸性粒细胞、巨噬细胞、中性粒细胞、NK CD56 细胞、NK 细胞、浆细胞样树突状细胞(pDCs)、辅助性 T 细胞和 T 效应记忆(Tem)细胞的浸润显著相关。此外,高 GPR37 表达与 M2 巨噬细胞浸润增加呈正相关,而 M2 巨噬细胞浸润与预后不良相关。此外,GPR37 与多种免疫检查点(ICPs)呈正相关。最后,GPR37 启动子的低甲基化与神经胶质瘤中高表达水平和预后不良相关。
GPR37 在神经胶质瘤中具有诊断和预后价值。GPR37 的可能生物学机制为神经胶质瘤的临床诊断和治疗提供了新的见解。