Guan Yiming, Xu Bing, Sui Yi, Li Hui, Chen Zhezhou, Luan Yu, Yang Ruijia, Qi Wanshun, Guan Qi
Faculty of Medical Laboratory Science, Ruijin Hospital,, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Neurology, The First People's Hospital of Shenyang (Shenyang Brain Hospital), Shenyang Medical College, Shenyang, China.
J Mol Neurosci. 2023 Mar;73(2-3):143-158. doi: 10.1007/s12031-023-02104-3. Epub 2023 Feb 7.
Cytohesin-4 (CYTH4) is a member of the PSCD family. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. In previous studies, CYTH4 has been linked with multiple brain diseases, but not glioma, the most common type of brain tumor. We utilized multiple glioma single-cell RNA sequencing datasets and bulk data from the TCGA and CGGA and conducted GSEA and KEGG and GO analyses. Biomarker potential was tested via ROC curve analysis. Radar plots were used to study TMB and MSI correlations. Immune cell studies were conducted using CIBERSORT. All statistical analyses were performed in R software and GraphPad Prism 9. CYTH4 was overexpressed in the glioma macrophage population in several single-cell RNA sequencing datasets and was most correlated with M2 macrophages. CYTH4 expression was higher in tumor tissues and was correlated with survival and WHO grade. ROC curves suggested CYTH4 overexpression to be a potential glioma biomarker. GSEA results indicated a relationship between CYTH4 and apoptosis, and PPI analysis supported a pyroptosis correlation. KEGG and GO analysis results linked CYTH4 with antigen processing and presentation and neutrophil activities. In summary, the study identified a CYTH4/pyroptosis/M2 macrophage axis. CYTH4 was upregulated in M2 macrophages in glioma and affected pyroptosis. CYTH4 overexpression is a potential biomarker predicting a poor prognosis.
细胞衔接蛋白4（CYTH4）是PSCD家族的成员。该家族成员似乎介导蛋白质分选和膜运输的调节。在先前的研究中，CYTH4与多种脑部疾病有关，但与最常见的脑肿瘤类型胶质瘤无关。我们利用了多个胶质瘤单细胞RNA测序数据集以及来自TCGA和CGGA的批量数据，并进行了基因集富集分析（GSEA）、京都基因与基因组百科全书（KEGG）分析和基因本体论（GO）分析。通过ROC曲线分析测试生物标志物潜力。使用雷达图研究肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）的相关性。使用CIBERSORT进行免疫细胞研究。所有统计分析均在R软件和GraphPad Prism 9中进行。在几个单细胞RNA测序数据集中，CYTH4在胶质瘤巨噬细胞群体中过表达，并且与M2巨噬细胞相关性最高。CYTH4在肿瘤组织中表达较高，并且与生存率和世界卫生组织（WHO）分级相关。ROC曲线表明CYTH4过表达是一种潜在的胶质瘤生物标志物。GSEA结果表明CYTH4与细胞凋亡之间存在关联，蛋白质-蛋白质相互作用（PPI）分析支持与细胞焦亡的相关性。KEGG和GO分析结果将CYTH4与抗原加工和呈递以及中性粒细胞活性联系起来。总之，该研究确定了一个CYTH4/细胞焦亡/M2巨噬细胞轴。CYTH4在胶质瘤的M2巨噬细胞中上调并影响细胞焦亡。CYTH4过表达是预测预后不良的潜在生物标志物。
