目的:胶质母细胞瘤(GBM)是一种侵袭性原发性脑肿瘤,5年生存率低于5%。治疗反应评估可能是具有挑战性的,因为在临床上和在成像上模拟真实肿瘤进展的炎性假性进展。开发额外的非侵入性检测是至关重要的。在这篇文章中,作者回顾了可用于开发GBM液体活检的各种生物标志物,除了优势,局限性,未来的应用。此外,他们提出了一种潜在的液体活检设计,该设计基于靶向非肿瘤性细胞外囊泡的基于细胞外囊泡的液体活检.
方法:作者通过检索PubMed,Scopus,和谷歌学者数据库。文章评估了生物标志物的类型,隔离方法,分析技术,和临床相关性。
结果:最近的工作表明,血浆的液体活检,血,和/或CSF有望作为可用于诊断复发的非侵入性临床工具,评估治疗反应,并预测GBM患者的预后。GBM的液体活检主要集中在细胞外囊泡,无细胞肿瘤核酸,和全细胞分离物作为局灶性生物标志物。GBM肿瘤特征是通过分析肿瘤基因突变产生的,独特的RNA表达,以及代谢和蛋白质组学改变。液体活检捕获肿瘤异质性,识别可能无法通过手术活检标本检测到的GBM肿瘤的改变。最后,生物标志物负荷可用于评估GBM的治疗反应和复发。
结论:液体活检为无侵入性手术监测GBM的治疗反应和复发提供了一个有希望的途径。尽管必须采取额外的措施将液体活检带入诊所,原理验证研究和隔离方法是有希望的。最终,CSF和/或基于血浆的液体活检可能是神经外科医生在不久的将来治疗和管理GBM患者的有力工具。
Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle-based liquid biopsy targeting nonneoplastic extracellular vesicles.
The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance.
Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM.
Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon\'s arsenal in the near future for the treatment and management of GBM patients.