胶质母细胞瘤的代谢重塑:一项纵向多组学研究。

IF 6.2 2区 医学 Q1 NEUROSCIENCES
Maxime Fontanilles, Jean-David Heisbourg, Arthur Daban, Frederic Di Fiore, Louis-Ferdinand Pépin, Florent Marguet, Olivier Langlois, Cristina Alexandru, Isabelle Tennevet, Franklin Ducatez, Carine Pilon, Thomas Plichet, Déborah Mokbel, Céline Lesueur, Soumeya Bekri, Abdellah Tebani
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引用次数: 0

摘要

利用无创液体活检监测肿瘤演变和预测生存期是胶质母细胞瘤患者尚未满足的需求。蛋白质组学和代谢组学血液分析时代的到来可能会对此有所帮助。我们开展了一项病例对照研究。患者被纳入GLIOPLAK试验(ClinicalTrials.gov Identifier:NCT02617745),这是一项前瞻性双中心研究,于2015年11月至2022年12月期间进行。患者只接受活组织检查,并接受放疗和替莫唑胺治疗。在三个不同的时间点采集血液样本:同时接受放化疗前后和肿瘤进展时。利用代谢组学和蛋白质组学对患者和对照组的血浆样本进行了分析,得出了371个omics特征。研究人员进行了描述性、差异性和预测性分析,以评估血浆全能组学特征水平与患者预后之间的关系。此外,还分析了诊断性能和纵向变化。研究包括 67 名受试者(34 名患者和 33 名对照组)。在患者和对照组之间观察到代谢物和蛋白质的表达存在明显差异。使用 omics 特征的预测模型在区分患者和对照组方面显示出很高的准确性。纵向分析揭示了一些全息特征的时间变化,包括CD22、CXCL13、EGF、IL6、GZMH、KLK4和TNFRSP6B。生存分析确定了77个与OS显著相关的全息特征,其中ERBB2和ITGAV在所有时间点都与OS相关。通路分析揭示了参与胶质母细胞瘤进展的动态致癌通路。这项研究揭示了血浆全息特征作为胶质母细胞瘤诊断、进展和总生存期生物标志物的潜力。现在应该在专门的前瞻性试验中探索其临床意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolic remodeling in glioblastoma: a longitudinal multi-omics study.

Monitoring tumor evolution and predicting survival using non-invasive liquid biopsy is an unmet need for glioblastoma patients. The era of proteomics and metabolomics blood analyzes, may help in this context. A case-control study was conducted. Patients were included in the GLIOPLAK trial (ClinicalTrials.gov Identifier: NCT02617745), a prospective bicentric study conducted between November 2015 and December 2022. Patients underwent biopsy alone and received radiotherapy and temozolomide. Blood samples were collected at three different time points: before and after concomitant radiochemotherapy, and at the time of tumor progression. Plasma samples from patients and controls were analyzed using metabolomics and proteomics, generating 371 omics features. Descriptive, differential, and predictive analyses were performed to assess the relationship between plasma omics feature levels and patient outcome. Diagnostic performance and longitudinal variations were also analyzed. The study included 67 subjects (34 patients and 33 controls). A significant differential expression of metabolites and proteins between patients and controls was observed. Predictive models using omics features showed high accuracy in distinguishing patients from controls. Longitudinal analysis revealed temporal variations in a few omics features including CD22, CXCL13, EGF, IL6, GZMH, KLK4, and TNFRSP6B. Survival analysis identified 77 omics features significantly associated with OS, with ERBB2 and ITGAV consistently linked to OS at all timepoints. Pathway analysis revealed dynamic oncogenic pathways involved in glioblastoma progression. This study provides insights into the potential of plasma omics features as biomarkers for glioblastoma diagnosis, progression and overall survival. Clinical implication should now be explored in dedicated prospective trials.

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来源期刊
Acta Neuropathologica Communications
Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine
CiteScore
11.20
自引率
2.80%
发文量
162
审稿时长
8 weeks
期刊介绍: "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.
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