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基于机器学习识别糖基转移酶相关mRNA以改善胶质瘤的预后和抗肿瘤治疗反应

Machine learning-based identification of glycosyltransferase-related mRNAs for improving outcomes and the anti-tumor therapeutic response of gliomas.

作者信息

Zhang Chunyu, Zhou Wei

机构信息

School of Medicine, Tongji University, Shanghai, China.

Department of Anesthesiology, Huzhou Central Hospital, The Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, Zhejiang, China.

出版信息

Front Pharmacol. 2023 Aug 16;14:1200795. doi: 10.3389/fphar.2023.1200795. eCollection 2023.

Abstract

Glycosyltransferase participates in glycosylation modification, and glycosyltransferase alterations are involved in carcinogenesis, progression, and immune evasion, leading to poor outcomes. However, in-depth studies on the influence of glycosyltransferase on clinical outcomes and treatments are lacking. The analysis of differentially expressed genes was performed using the Gene Expression Profiling Interactive Analysis 2 database. A total of 10 machine learning algorithms were introduced, namely, random survival forest, elastic network, least absolute shrinkage and selection operator, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox, supervised principal components, generalized boosted regression modeling, and survival support vector machine. Gene Set Enrichment Analysis was performed to explore signaling pathways regulated by the signature. Cell-type identification by estimating relative subsets of RNA transcripts was used for estimating the fractions of immune cell types. Here, we analyzed the genomic and expressive alterations in glycosyltransferase-related genes in gliomas. A combination of 80 machine learning algorithms was introduced to establish the glycosyltransferase-related mRNA signature (GRMS) based on 2,030 glioma samples from The Cancer Genome Atlas Program, Chinese Glioma Genome Atlas, Rembrandt, Gravendeel, and Kamoun cohorts. The GRMS was identified as an independent hazardous factor for overall survival and exhibited stable and robust performance. Notably, gliomas in the high-GRMS subgroup exhibited abundant tumor-infiltrating lymphocytes and tumor mutation burden values, increased expressive levels of hepatitis A virus cellular receptor 2 and CD274, and improved progression-free survival when subjected to anti-tumor immunotherapy. The GRMS may act as a powerful and promising biomarker for improving the clinical prognosis of glioma patients.

摘要

糖基转移酶参与糖基化修饰,糖基转移酶的改变与肿瘤发生、进展和免疫逃逸有关,导致不良预后。然而,目前缺乏关于糖基转移酶对临床结局和治疗影响的深入研究。使用基因表达谱交互式分析2数据库进行差异表达基因分析。共引入了10种机器学习算法,即随机生存森林、弹性网络、最小绝对收缩和选择算子、岭回归、逐步Cox回归、CoxBoost、Cox偏最小二乘回归、监督主成分分析、广义增强回归建模和生存支持向量机。进行基因集富集分析以探索由特征调控的信号通路。通过估计RNA转录本的相对子集进行细胞类型鉴定,以估计免疫细胞类型的比例。在此,我们分析了胶质瘤中糖基转移酶相关基因的基因组和表达改变。基于来自癌症基因组图谱计划、中国胶质瘤基因组图谱、伦勃朗、格拉文德尔和卡蒙队列的2030个胶质瘤样本,引入80种机器学习算法的组合,建立了糖基转移酶相关mRNA特征(GRMS)。GRMS被确定为总生存的独立危险因素,表现出稳定且强大的性能。值得注意的是,高GRMS亚组的胶质瘤表现出丰富的肿瘤浸润淋巴细胞和肿瘤突变负荷值,甲型肝炎病毒细胞受体2和CD274的表达水平增加,并且在接受抗肿瘤免疫治疗时无进展生存期得到改善。GRMS可能作为一种强大且有前景的生物标志物,用于改善胶质瘤患者的临床预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1605/10468601/184a60cb417f/fphar-14-1200795-g001.jpg

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