Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Adv Exp Med Biol. 2020;1257:95-105. doi: 10.1007/978-3-030-43032-0_9.
Liquid biopsies encompass a number of new technologies designed to derive tumor data through the minimally invasive sampling of an accessible body fluid. These technologies remain early in their clinical development, and applications for patients with osteosarcoma are actively under investigation. In this chapter, we outline the current state of liquid biopsy technologies as they apply to cancer generally and osteosarcoma specifically, focusing on assays that detect and profile circulating tumor DNA (ctDNA), microRNAs (miRNA), and circulating tumor cells (CTCs). At present, ctDNA assays are the most mature, with multiple assays demonstrating the feasibility of detecting and quantifying ctDNA from blood samples of patients with osteosarcoma. Initial studies show that ctDNA can be detected in the majority of patients with osteosarcoma and that the detection and level of ctDNA correlates with a worse prognosis. Profiling of ctDNA can also identify specific somatic events that may have prognostic relevance, such as 8q gain in osteosarcoma. miRNAs are stable RNAs that regulate gene expression and are known to be dysregulated in cancer, and patterns of miRNA expression have been evaluated in multiple studies of patients with osteosarcoma. While studies have identified differential expression of many miRNAs in osteosarcomas compared to healthy controls, a consensus set of prognostic miRNAs has yet to be definitively validated. Recent studies have also demonstrated the feasibility of capturing CTCs in patients with osteosarcoma. The development of assays that quantify and profile CTCs for use as prognostic biomarkers or tools for biologic discovery is still in development. However, CTC technology holds incredible promise given the potential to perform multi-omic approaches in single cancer cells to understand osteosarcoma heterogeneity and tumor evolution. The next step required to move liquid biopsy technologies closer to helping patients will be wide-scale collection of patient samples from large prospective studies.
液体活检涵盖了许多旨在通过对可及体液的微创取样来获取肿瘤数据的新技术。这些技术仍处于临床开发的早期阶段，针对骨肉瘤患者的应用正在积极研究中。在本章中，我们概述了液体活检技术的现状，包括它们在癌症和骨肉瘤中的应用，重点介绍了检测和分析循环肿瘤 DNA（ctDNA）、微小 RNA（miRNA）和循环肿瘤细胞（CTC）的检测方法。目前，ctDNA 检测方法最为成熟，多项检测方法证明了从骨肉瘤患者的血液样本中检测和定量 ctDNA 的可行性。初步研究表明，ctDNA 可以在大多数骨肉瘤患者中检测到，ctDNA 的检测和水平与预后较差相关。ctDNA 的分析还可以识别具有预后相关性的特定体细胞事件，例如骨肉瘤中的 8q 增益。miRNA 是调节基因表达的稳定 RNA，已知在癌症中失调，并且已经在多项骨肉瘤患者的研究中评估了 miRNA 的表达模式。虽然研究已经确定了与健康对照相比，骨肉瘤中许多 miRNA 的表达存在差异，但尚未明确验证具有预后意义的 miRNA 的一致集。最近的研究还证明了在骨肉瘤患者中捕获 CTC 的可行性。用于将 CTC 定量和分析为预后生物标志物或用于生物学发现的工具的检测方法的开发仍在进行中。然而，CTC 技术具有巨大的潜力，因为它有可能在单个癌细胞中进行多组学方法，以了解骨肉瘤异质性和肿瘤演变，因此有望成为一项极具前途的技术。将液体活检技术推向更贴近患者的下一步将是从大型前瞻性研究中广泛收集患者样本。
