Taori Suchet, Habib Ahmed, Adida Samuel, Gecici Neslihan Nisa, Sharma Nikhil, Calcaterra Michael, Tang Anthony, Pandya Sumaarg, Mehra Arnav, Deng Hansen, Elidrissy Hayat, Idrissi Yassine Alami, Amjadzadeh Mohammadreza, Zinn Pascal O
School of Medicine, University of Pittsburgh, Pennsylvania, PA, USA.
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pennsylvania, PA, USA.
J Neurooncol. 2025 Mar;172(1):41-49. doi: 10.1007/s11060-024-04903-z. Epub 2024 Dec 13.
High-grade gliomas (HGG) represent a challenging subset of brain tumors characterized by aggressive nature and poor prognosis. Histopathology remains to be the standard for diagnosis, however, it is invasive, prone to sampling errors, and may not capture the full tumor heterogeneity and evolution over time. In recent years, there has been a growing interest in the potential utility of circulating biomarkers, obtained through minimally-invasive liquid biopsies, providing an opportunity for diagnosis, prognostication, monitoring treatment response and developing targeted therapies.
We have reviewed the literature on circulating biomarkers for HGG, including circulating tumor cells (CTCs), circulating tumor-derived exosomes/extracellular vesicles (ctEVs), circulating tumor-derived DNA (ctDNA), circulating tumor-derived miRNA (ctmiRNA), and circulating tumor-derived proteins.
CTCs provide real-time information about tumor characteristics for molecular profiling and monitoring treatment response, yet their low numbers in circulation makes detection challenging. ctEVs carry a range of biomolecules and are easily detectable. However, they are not exclusively released from tumor cells and heterogeneity in their content requires standardized isolation and analysis methods. ctDNA is another promising biomarker with its levels correlating with the disease stage. However, its low concentration in blood requires highly sensitive techniques for identification and differentiation from normal cell-free DNA. ctmiRNA and tumor-derived proteins show promise but are limited by their susceptibility to dilution and lack of specificity in current technology.
This review highlights the transformative potential of circulating biomarkers in the management of HGG, with implications for improving patient outcomes, optimizing treatment strategies, and advancing precision oncology in neuro-oncology practice.
高级别胶质瘤（HGG）是一类具有挑战性的脑肿瘤，其特点是侵袭性强且预后不良。组织病理学仍是诊断的标准，但它具有侵入性，容易出现取样误差，并且可能无法捕捉肿瘤的全部异质性以及随时间的演变。近年来，通过微创液体活检获得的循环生物标志物的潜在效用受到越来越多的关注，这为诊断、预后评估、监测治疗反应以及开发靶向治疗提供了机会。
我们回顾了关于HGG循环生物标志物的文献，包括循环肿瘤细胞（CTC）、循环肿瘤来源的外泌体/细胞外囊泡（ctEV）、循环肿瘤来源的DNA（ctDNA）、循环肿瘤来源的miRNA（ctmiRNA）和循环肿瘤来源的蛋白质。
CTC为分子谱分析和监测治疗反应提供了有关肿瘤特征的实时信息，然而其在循环中的数量较少，使得检测具有挑战性。ctEV携带一系列生物分子，易于检测。然而，它们并非仅由肿瘤细胞释放，其内容物的异质性需要标准化的分离和分析方法。ctDNA是另一种有前景的生物标志物，其水平与疾病阶段相关。然而，其在血液中的低浓度需要高灵敏度技术来识别并与正常游离DNA区分开来。ctmiRNA和肿瘤来源的蛋白质显示出前景，但受到其易被稀释以及当前技术缺乏特异性的限制。
本综述强调了循环生物标志物在HGG管理中的变革潜力，对改善患者预后、优化治疗策略以及推进神经肿瘤学实践中的精准肿瘤学具有重要意义。
