Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-03-16 DOI:10.1111/cns.70330

Zhipeng Jiang, Hanxue Huang, Youwei Guo, Zihan Wang, Hailong Huang, Wen Yin, Haoxuan Huang, Lei Wang, Weidong Liu, Xingjun Jiang, Caiping Ren

{"title":"Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis","authors":"Zhipeng Jiang, Hanxue Huang, Youwei Guo, Zihan Wang, Hailong Huang, Wen Yin, Haoxuan Huang, Lei Wang, Weidong Liu, Xingjun Jiang, Caiping Ren","doi":"10.1111/cns.70330","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Gliomas represent the most aggressive malignancies of the central nervous system, with posttranslational modifications (PTMs) emerging as critical regulators of oncogenic processes through dynamic protein functional modulation. Despite their established role in tumor biology, the systematic characterization of PTM-mediated molecular mechanisms driving glioma progression remains unexplored. This study aims to uncover the molecular mechanisms of glioma, with a focus on the role of PTMs.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We analyzed the PTM pathway to classify glioma patients into distinct clusters. Comprehensive analyses compared intercluster differences in clinical outcomes, mutational landscapes, and immune microenvironment profiles. Differentially expressed genes (DEGs) were identified to construct a robust prognostic prediction model with machine learning approaches. Among the genes included in the model, <i>TOM1L1</i> (Target of Myb1 Like 1 Membrane Trafficking Protein) was selected for in vitro experimental validation to assess its role in glioma progression.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>PTMs were found to influence glioma prognosis significantly. Dysregulation in specific pathways, such as glutathionylation and citrullination, was correlated with more aggressive clinical features. The prognostic model, comprising DEGs such as <i>TOM1L1</i>, demonstrated high predictive accuracy (c-index = 0.867)—the scores derived from the model strongly correlated with glioma progression indicators. In vitro experiments revealed that TOM1L1 facilitates malignant progression by modulating PTM pathways, confirming its functional role in glioma.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our study establishes the first comprehensive PTM atlas in gliomas, revealing subtype-specific modification patterns with clinical and therapeutic implications. <i>TOM1L1</i> emerges as a promising prognostic biomarker and a potential therapeutic intervention target. Targeting PTM pathways may offer novel strategies for glioma treatment, enhancing patient outcomes.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70330","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70330","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Gliomas represent the most aggressive malignancies of the central nervous system, with posttranslational modifications (PTMs) emerging as critical regulators of oncogenic processes through dynamic protein functional modulation. Despite their established role in tumor biology, the systematic characterization of PTM-mediated molecular mechanisms driving glioma progression remains unexplored. This study aims to uncover the molecular mechanisms of glioma, with a focus on the role of PTMs.

Methods

We analyzed the PTM pathway to classify glioma patients into distinct clusters. Comprehensive analyses compared intercluster differences in clinical outcomes, mutational landscapes, and immune microenvironment profiles. Differentially expressed genes (DEGs) were identified to construct a robust prognostic prediction model with machine learning approaches. Among the genes included in the model, TOM1L1 (Target of Myb1 Like 1 Membrane Trafficking Protein) was selected for in vitro experimental validation to assess its role in glioma progression.

Results

PTMs were found to influence glioma prognosis significantly. Dysregulation in specific pathways, such as glutathionylation and citrullination, was correlated with more aggressive clinical features. The prognostic model, comprising DEGs such as TOM1L1, demonstrated high predictive accuracy (c-index = 0.867)—the scores derived from the model strongly correlated with glioma progression indicators. In vitro experiments revealed that TOM1L1 facilitates malignant progression by modulating PTM pathways, confirming its functional role in glioma.

Conclusion

Our study establishes the first comprehensive PTM atlas in gliomas, revealing subtype-specific modification patterns with clinical and therapeutic implications. TOM1L1 emerges as a promising prognostic biomarker and a potential therapeutic intervention target. Targeting PTM pathways may offer novel strategies for glioma treatment, enhancing patient outcomes.

Abstract Image

查看原文本刊更多论文

揭示蛋白质翻译后修饰在胶质瘤预后中的作用

神经胶质瘤是中枢神经系统最具侵袭性的恶性肿瘤，翻译后修饰（PTMs）通过动态蛋白功能调节成为致癌过程的关键调节因子。尽管ptm在肿瘤生物学中具有既定的作用，但ptm介导的驱动胶质瘤进展的分子机制的系统表征仍未被探索。本研究旨在揭示胶质瘤的分子机制，重点研究PTMs的作用。方法通过PTM通路对胶质瘤患者进行分类。综合分析比较了簇间临床结果、突变景观和免疫微环境概况的差异。鉴别差异表达基因（DEGs），利用机器学习方法构建稳健的预后预测模型。在模型中包含的基因中，选择TOM1L1 （Myb1 Like 1膜运输蛋白靶蛋白）进行体外实验验证，以评估其在胶质瘤进展中的作用。结果发现ptm对胶质瘤的预后有显著影响。特定途径的失调，如谷胱甘肽化和瓜氨酸化，与更具侵袭性的临床特征相关。由诸如TOM1L1等deg组成的预后模型显示出很高的预测准确性（c-index = 0.867），该模型得出的评分与胶质瘤进展指标密切相关。体外实验显示TOM1L1通过调节PTM通路促进恶性进展，证实了其在胶质瘤中的功能作用。结论本研究首次建立了脑胶质瘤的PTM图谱，揭示了具有临床和治疗意义的亚型特异性修饰模式。TOM1L1是一种有前景的预后生物标志物和潜在的治疗干预靶点。靶向PTM通路可能为胶质瘤治疗提供新的策略，提高患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.