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用于监测成人胶质瘤和脑转移瘤的液体活检

Liquid biopsies for the monitoring of gliomas and brain metastases in adults.

作者信息

Dwarshuis Govert, Kroon Lente L, Brandsma Dieta, Noske David P, Best Myron G, Sol Nik

机构信息

Department of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Department of Neurology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, Amsterdam, The Netherlands.

出版信息

Acta Neuropathol. 2025 Apr 26;149(1):37. doi: 10.1007/s00401-025-02880-9.

DOI:10.1007/s00401-025-02880-9
PMID:40285800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12033197/
Abstract

Clinical evaluation and MR imaging are currently the cornerstone of brain tumor progression monitoring. However, this is complicated by the occurrence of treatment effects such as pseudoprogression and radionecrosis. While essential for patient management, the distinction from true progression remains a significant challenge. Moreover, MR imaging provides limited real-time insights into tumor heterogeneity, genetic divergence, and treatment resistance. Although surgical histopathological biopsies can yield additional valuable information, they are not always conclusive, invasive, and therefore, not suitable for longitudinal measurements. In the era of precision medicine, there is a critical need for minimally invasive, accurate, and cost-effective monitoring methods for both primary brain tumors and brain metastases. Liquid biopsies have emerged as a potential candidate. Various analytes, including circulating nucleic acids, extracellular vesicles, platelet RNAs, and circulating tumor cells, can be obtained from whole blood and its derivatives, as well as other body fluids such as cerebrospinal fluid. In this narrative review, we outline the potential of liquid biopsies for the management of gliomas and brain metastases in adults and emphasize their utility in monitoring disease progression and treatment response. We discuss the most studied biofluids and analytes, along with their respective advantages and downsides. Furthermore, we address key considerations for future research and biobanking to pave the way for clinical implementation.

摘要

临床评估和磁共振成像(MR)目前是脑肿瘤进展监测的基石。然而,诸如假性进展和放射性坏死等治疗效应的出现使这一过程变得复杂。虽然对于患者管理至关重要,但将其与真正的进展区分开来仍然是一项重大挑战。此外,MR成像对肿瘤异质性、基因差异和治疗抵抗的实时洞察有限。尽管手术组织病理活检可以提供额外的有价值信息,但它们并不总是具有决定性意义,具有侵入性,因此不适合进行纵向测量。在精准医学时代,对于原发性脑肿瘤和脑转移瘤,迫切需要微创、准确且经济高效的监测方法。液体活检已成为一个潜在的候选方法。可以从全血及其衍生物以及其他体液(如脑脊液)中获取各种分析物,包括循环核酸、细胞外囊泡、血小板RNA和循环肿瘤细胞。在这篇叙述性综述中,我们概述了液体活检在成人间胶质瘤和脑转移瘤管理中的潜力,并强调其在监测疾病进展和治疗反应方面的效用。我们讨论了研究最多的生物流体和分析物,以及它们各自的优缺点。此外,我们阐述了未来研究和生物样本库的关键考虑因素,以为临床应用铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ceb/12033197/2b3359dbe1a3/401_2025_2880_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ceb/12033197/ef6e6ec52d34/401_2025_2880_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ceb/12033197/2b3359dbe1a3/401_2025_2880_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ceb/12033197/ef6e6ec52d34/401_2025_2880_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ceb/12033197/2b3359dbe1a3/401_2025_2880_Fig2_HTML.jpg

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本文引用的文献

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Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients.更高的游离DNA产量对胶质母细胞瘤患者液体活检检测的影响
Clin Chem. 2025 Jan 3;71(1):215-225. doi: 10.1093/clinchem/hvae178.
2
Longitudinal Glioma Monitoring via Cerebrospinal Fluid Cell-Free DNA.通过脑脊液游离DNA进行胶质瘤纵向监测。
Clin Cancer Res. 2025 Mar 3;31(5):881-889. doi: 10.1158/1078-0432.CCR-24-1814.
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Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients.从脑肿瘤患者的脑脊液游离 DNA 中检测诊断性体细胞拷贝数改变。
Acta Neuropathol Commun. 2024 Nov 20;12(1):177. doi: 10.1186/s40478-024-01887-9.
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Prediction of brain metastasis development with DNA methylation signatures.利用DNA甲基化特征预测脑转移瘤的发展
Nat Med. 2025 Jan;31(1):116-125. doi: 10.1038/s41591-024-03286-y. Epub 2024 Oct 8.
5
Glioblastoma, IDH-wildtype with primarily leptomeningeal localization diagnosed by nanopore sequencing of cell-free DNA from cerebrospinal fluid.通过脑脊液游离DNA的纳米孔测序诊断出的原发性软脑膜定位的异柠檬酸脱氢酶野生型胶质母细胞瘤。
Acta Neuropathol. 2024 Sep 3;148(1):35. doi: 10.1007/s00401-024-02792-0.
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Deconvolution of the tumor-educated platelet transcriptome reveals activated platelet and inflammatory cell transcript signatures.肿瘤诱导血小板转录组学的去卷积揭示了激活的血小板和炎症细胞的转录特征。
JCI Insight. 2024 Aug 27;9(19):e178719. doi: 10.1172/jci.insight.178719.
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Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas.用于检测 IDH1.R132H 突变型脑胶质瘤的血液检测的临床效用。
Nat Commun. 2024 Aug 16;15(1):7074. doi: 10.1038/s41467-024-51332-7.
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Nat Commun. 2024 May 29;15(1):4549. doi: 10.1038/s41467-024-48740-0.
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