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一种糖基化相关基因特征可预测胶质瘤的预后、免疫微环境浸润及药物敏感性。

A glycosylation-related gene signature predicts prognosis, immune microenvironment infiltration, and drug sensitivity in glioma.

作者信息

Yang Yanbo, Teng Haiying, Zhang Yulian, Wang Fei, Tang Liyan, Zhang Chuanpeng, Hu Ziyi, Chen Yuxuan, Ge Yi, Wang Zhong, Yu Yanbing

机构信息

China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

出版信息

Front Pharmacol. 2024 Jan 16;14:1259051. doi: 10.3389/fphar.2023.1259051. eCollection 2023.

Abstract

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (, , , , and ) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.

摘要

胶质瘤是成人中枢神经系统最常见的原发性癌症。糖基化是真核细胞中普遍存在的一种翻译后修饰,会导致蛋白质发生多种修饰。我们从癌症基因组图谱(TCGA)、中国胶质瘤基因组图谱(CGGA)、基因表达综合数据库(GEO)和分子脑肿瘤数据储存库(Rembrandt)数据库中获取了临床信息、批量RNA测序数据和单细胞RNA测序(scRNA-seq)数据。正常脑组织的RNA测序数据来自基因型-组织表达(GTEx)数据库。然后,鉴定出差异表达的糖基化基因,并使用最小绝对收缩和选择算子(LASSO)正则化Cox模型进一步进行变量选择。我们进一步进行了富集分析、qPCR、列线图和单细胞转录组分析以检测糖基化特征。还进行了药物敏感性分析。一个由五个基因组成的糖基化特征(、、、和)将患者分为低风险或高风险组。生存分析、qPCR、ROC曲线和分层分析显示高风险组的预后较差。此外,基因集富集分析(GSEA)和免疫浸润分析表明,糖基化特征有可能预测胶质瘤中的免疫反应。此外,四种药物(克唑替尼、拉帕替尼、尼洛替尼和拓扑替康)在两个风险组之间表现出不同的反应。基于单细胞表达谱,胶质瘤细胞已被分为七类。这五个基因的糖基化特征可以准确预测胶质瘤的预后,并可能为免疫治疗提供额外的指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f3/10824914/725d8afd309d/fphar-14-1259051-g001.jpg

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