doi:10.3969/j.issn.1004-583X.2026.08.013

Abstract

CLC Number:

R738.1

Add to citation manager EndNote|Ris|BibTeX

URL: https://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2026.08.013

https://www.lchc.cn/EN/Y2026/V41/I8/747

Figures/Tables 2

References 57

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263.doi:10.3322/caac.21834.
[2]	Xi Y, Qiao L, Na B, et al. Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015[J]. Chin Med J (Engl), 2023, 136(17):2037-2043.doi:10.1097/CM9.0000000000002590.
[3]	Guedes A, Oliveira MBDR, Melo A, et al. Update in imaging evaluation of bone and soft tissue sarcomas[J]. Rev Bras Ortop (Sao Paulo), 2023, 58(2):179-190.doi:10.1055/s-0043-1765010.
[4]	Cazzato RL, Garnon J, Jennings JW, et al. Interventional management of malignant bone tumours[J]. J Med Imaging Radiat Oncol, 2023, 67(8):862-869.doi:10.1111/1754-9485.13587.
[5]	Aiyer S, Kim TH, Collier K, et al. Unlocking the potential of ctDNA in sarcomas: A review of recent advances[J]. Cancers (Basel), 2025, 17(6):1040.doi:10.3390/cancers17061040.
[6]	Stejskal P, Goodarzi H, Srovnal J, et al. Circulating tumor nucleic acids: Biology, release mechanisms, and clinical relevance[J]. Mol Cancer, 2023, 22(1):15.doi:10.1186/s12943-022-01710-w. pmid: 36681803
[7]	Tsoi KM, Gokgoz N, Darville-O'Quinn P, et al. Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas[J]. Bone Joint Res, 2021, 10(9):602-610.doi:10.1302/2046-3758.109.BJR-2020-0290.R1. pmid: 34558310
[8]	Turabi K, Klute K, Radhakrishnan P. Decoding the dynamics of circulating tumor DNA in liquid biopsies[J]. Cancers (Basel), 2024, 16(13):2432.doi:10.3390/cancers16132432.
[9]	Udomruk S, Phanphaisarn A, Kanthawang T, et al. Characterization of cell-free DNA size distribution in osteosarcoma patients[J]. Clin Cancer Res, 2023, 29(11):2085-2094.doi:10.1158/1078-0432.CCR-22-2912. pmid: 36735493
[10]	Bodlak A, Chang K, Channel J, et al. Circulating plasma tumor DNA is superior to plasma tumor RNA detection in Ewing sarcoma patients: ptDNA and ptRNA in Ewing sarcoma[J]. J Mol Diagn, 2021, 23(7):872-881.doi:10.1016/j.jmoldx.2021.04.003. pmid: 33887462
[11]	Tian B, Chen X, Zheng J, et al. Liquid biopsy in malignant primary bone tumors: Clinical applications of circulating tumor DNA and circulating tumor cells for diagnosis, prognosis and treatment monitoring (Review)[J]. Oncol Rep, 2026, 55(4):72.doi:10.3892/or.2026.9077.
[12]	Wang Y, Fujiwara T, Kurozumi T, et al. Advances in liquid biopsy for bone and soft-tissue sarcomas[J]. Int J Clin Oncol, 2025, 30(9):1722-1733.doi:10.1007/s10147-025-02813-2. pmid: 40679665
[13]	Smolle MA, Seidel MG, Kashofer K, et al. Precision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: A systematic review[J]. Arch Orthop Trauma Surg, 2025, 145(1):121.doi:10.1007/s00402-024-05711-w.
[14]	Seidel MG, Kashofer K, Moser T, et al. Clinical implementation of plasma cell-free circulating tumor DNA quantification by digital droplet PCR for the monitoring of Ewing sarcoma in children and adolescents[J]. Front Pediatr, 2022, 10:926405.doi:10.3389/fped.2022.926405.
[15]	Lyskjær I, Kara N, De Noon S, et al. Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA[J]. Eur J Cancer, 2022, 168:1-11.doi:10.1016/j.ejca.2022.03.013. pmid: 35421838
[16]	Lianidou E. Detection and relevance of epigenetic markers on ctDNA: Recent advances and future outlook[J]. Mol Oncol, 2021, 15(7):1683-1700.doi:10.1002/1878-0261.13034.
[17]	Wang B, Wang M, Lin Y, et al. Circulating tumor DNA methylation: A promising clinical tool for cancer diagnosis and management[J]. Clin Chem Lab Med, 2024, 62(11):2111-2127.doi:10.1515/cclm-2023-1327. pmid: 38443752
[18]	Zhu Y, Chen J, Chen C, et al. Deciphering mechanical cues in the microenvironment: From non-malignant settings to tumor progression[J]. Biomark Res, 2025, 13(1):11.doi:10.1186/s40364-025-00727-9. pmid: 39849659
[19]	Di Pompo G, Cortini M, Baldini N, et al. Acid microenvironment in bone sarcomas[J]. Cancers (Basel), 2021, 13(13):3153.doi:10.3390/cancers13133153.
[20]	Serpas L, Chan RWY, Jiang P, et al. DNASE1L3 deletion causes aberrations in length and end-motif frequencies in plasma DNA[J]. Proc Natl Acad Sci U S A, 2019, 116(2):641-649.doi:10.1073/pnas.1814561116.
[21]	Stucker S, Chen J, Watt FE, et al. Bone angiogenesis and vascular niche remodeling in stress, aging, and diseases[J]. Front Cell Dev Biol, 2020, 8:602269.doi:10.3389/fcell.2020.602269.
[22]	Dalal S, Berry AM, Cullinane CJ, et al. Vascular endothelial growth factor: A therapeutic target for tumors of the Ewing's sarcoma family[J]. Clin Cancer Res, 2005, 11(6):2364-2378.doi:10.1158/1078-0432.CCR-04-1743. pmid: 15788688
[23]	Kurma K, Alix-Panabières C. Mechanobiology and survival strategies of circulating tumor cells: A process towards the invasive and metastatic phenotype[J]. Front Cell Dev Biol, 2023, 11:1188499.doi:10.3389/fcell.2023.1188499.
[24]	Pantel K, Alix-Panabières C, Hofman P, et al. Fostering the implementation of liquid biopsy in clinical practice: Meeting report 2024 of the European Liquid Biopsy Society (ELBS)[J]. J Exp Clin Cancer Res, 2025, 44(1):156.doi:10.1186/s13046-025-03398-4. pmid: 40410806
[25]	Lockwood CM, Merker JD, Bain E, et al. Towards preanalytical best practices for liquid biopsy studies: A BLOODPAC landscape analysis[J]. Clin Pharmacol Ther, 2025, 117(1):28-33.doi:10.1002/cpt.3416.
[26]	Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: A report from the ESMO Precision Medicine Working Group[J]. Ann Oncol, 2022, 33(8):750-768.doi:10.1016/j.annonc.2022.05.520. pmid: 35809752
[27]	Krumbholz M, Eiblwieser J, Ranft A, et al. Quantification of translocation-specific ctDNA provides an integrating parameter for early assessment of treatment response and risk stratification in Ewing sarcoma[J]. Clin Cancer Res, 2021, 27(21):5922-5930.doi:10.1158/1078-0432.CCR-21-1024. pmid: 34426444
[28]	Lee JS, Cho EH, Kim B, et al. Clinical practice guideline for blood-based circulating tumor DNA assays[J]. Ann Lab Med, 2024, 44(3):195-209.doi:10.3343/alm.2023.0389.
[29]	Sathyanarayana SH, Spracklin SB, Deharvengt SJ, et al. Standardized workflow and analytical validation of cell-free DNA extraction for liquid biopsy using a magnetic bead-based cartridge system[J]. Cells, 2025, 14(14):1062.doi:10.3390/cells14141062.
[30]	Pittella-Silva F, Chin YM, Chan HT, et al. Plasma or serum: Which is preferable for mutation detection in liquid biopsy?[J]. Clin Chem, 2020, 66(7):946-957.doi:10.1093/clinchem/hvaa090. pmid: 32516802
[31]	Andersson D, Kristiansson H, Luna Santamaría M, et al. Evaluation of automatic cell free DNA extraction metrics using different blood collection tubes[J]. Sci Rep, 2025, 15(1):19364.doi:10.1038/s41598-025-03508-4.
[32]	Lockwood CM, Borsu L, Cankovic M, et al. Recommendations for cell-free DNA assay validations: A joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists[J]. J Mol Diagn, 2023, 25(12):876-897.doi:10.1016/j.jmoldx.2023.09.004.
[33]	van der Leest P, Schuuring E. Critical factors in the analytical work flow of circulating tumor DNA-based molecular profiling[J]. Clin Chem, 2024, 70(1):220-233.doi:10.1093/clinchem/hvad194. pmid: 38175597
[34]	Romero A, Jantus-Lewintre E, García-Peláez B, et al. Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: Results of the RING observational trial[J]. Mol Oncol, 2021, 15(1):43-56.doi:10.1002/1878-0261.12864. pmid: 33107189
[35]	Takahashi N, Pongor L, Agrawal SP, et al. Genomic alterations and transcriptional phenotypes in circulating free DNA and matched metastatic tumor[J]. Genome Med, 2025, 17(1):15.doi:10.1186/s13073-025-01421-0. pmid: 40001151
[36]	Sundby RT, Pan A, Shern JF. Liquid biopsies in pediatric oncology: Opportunities and obstacles[J]. Curr Opin Pediatr, 2022, 34(1):39-47.doi:10.1097/MOP.0000000000001088.
[37]	Van Paemel R, Vandeputte C, Raman L, et al. The feasibility of using liquid biopsies as a complementary assay for copy number aberration profiling in routinely collected paediatric cancer patient samples[J]. Eur J Cancer, 2022, 160:12-23.doi:10.1016/j.ejca.2022.01.011.
[38]	van Dessel LF, Vitale SR, Helmijr JCA, et al. High-throughput isolation of circulating tumor DNA: A comparison of automated platforms[J]. Mol Oncol, 2019, 13(2):392-402.doi:10.1002/1878-0261.12477.
[39]	Deans ZC, Butler R, Cheetham M, et al. IQN path ASBL report from the first European cfDNA consensus meeting: Expert opinion on the minimal requirements for clinical ctDNA testing[J]. Virchows Arch, 2019, 474(6):681-689.doi:10.1007/s00428-019-02567-7.
[40]	Gutteridge A, Rathbone VM, Gibbons R, et al. Digital PCR analysis of circulating tumor DNA: A biomarker for chondrosarcoma diagnosis, prognostication, and residual disease detection[J]. Cancer Med, 2017, 6(9):2194-2202.doi:10.1002/cam4.1190.
[41]	Shukla NN, Patel JA, Magnan H, et al. Plasma DNA-based molecular diagnosis, prognostication, and monitoring of patients with EWSR1 fusion-positive sarcomas[J]. JCO Precis Oncol, 2017, 1:PO.16.00028.doi:10.1200/PO.16.00028.
[42]	Furukawa N, Hasegawa N, Kubota D, et al. Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours[J]. BMC Cancer, 2025, 25(1):587.doi:10.1186/s12885-025-12574-0. pmid: 40170158
[43]	Audinot B, Drubay D, Gaspar N, et al. ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: A translational study from the OS2006 trial[J]. Ann Oncol, 2024, 35(6):559-568.doi:10.1016/j.annonc.2023.12.006.
[44]	Shulman DS, Klega K, Imamovic-Tuco A, et al. Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: A report from the children's oncology group[J]. Br J Cancer, 2018, 119(5):615-621.doi:10.1038/s41416-018-0209-0.
[45]	Fu Y, Xu Y, Liu W, et al. Tumor-informed deep sequencing of ctDNA detects minimal residual disease and predicts relapse in osteosarcoma[J]. EClinicalMedicine, 2024, 73:102697.doi:10.1016/j.eclinm.2024.102697.
[46]	Eder JP, Doroshow DB, Do KT, et al. Clinical efficacy of olaparib in IDH1/IDH2-mutant mesenchymal sarcomas[J]. JCO Precis Oncol, 2021, 5:466-472.doi:10.1200/PO.20.00247.
[47]	Mu H, Zuo D, Chen J, et al. Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis[J]. Cancer Biol Med, 2022, 19(12):1397-1409.doi:10.20892/j.issn.2095-3941.2022.0109.
[48]	Green D, van Ewijk R, Tirtei E, et al. Biological sample collection to advance research and treatment: A fight osteosarcoma through European research and Euro Ewing consortium statement[J]. Clin Cancer Res, 2024, 30(15):3395-3406.doi:10.1158/1078-0432.CCR-23-3124.
[49]	Hayashi M, Zhu P, McCarty G, et al. Size-based detection of sarcoma circulating tumor cells and cell clusters[J]. Oncotarget, 2017, 8(45):78965-78977.doi:10.18632/oncotarget.20990. pmid: 29108279
[50]	Liu W, Long Q, Zhang W, et al. miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis[J]. Aging (Albany NY), 2021, 13(24):26414-26429.doi:10.18632/aging.203775.
[51]	Gally TB, Aleluia MM, Borges GF, et al. Circulating microRNAs as novel potential diagnostic biomarkers for osteosarcoma: A systematic review[J]. Biomolecules, 2021, 11(10):1432.doi:10.3390/biom11101432.
[52]	Georges S, Calleja LR, Jacques C, et al. Loss of miR-198 and -206 during primary tumor progression enables metastatic dissemination in human osteosarcoma[J]. Oncotarget, 2018, 9(55):30558-30573.doi:10.18632/oncotarget.25874.
[53]	Mouliere F, Smith CG, Heider K, et al. Fragmentation patterns and personalized analysis of circulating tumor DNA for early detection of pediatric cancers[J]. Cancer Discov, 2022, 12(3):754-773.doi:10.1158/2159-8290.CD-21-0860.
[54]	Keller L, Belloum Y, Wikman H, et al. Clinical relevance of blood-based ctDNA analysis: Mutation detection and beyond[J]. Br J Cancer, 2021, 124(2):345-358.doi:10.1038/s41416-020-01191-9.
[55]	Janssen FW, Lak NSM, Janda CY, et al. A comprehensive overview of liquid biopsy applications in pediatric solid tumors[J]. NPJ Precis Oncol, 2024, 8(1):172.doi:10.1038/s41698-024-00657-z. pmid: 39097671
[56]	Coppola CA, De Summa S, Matera G, et al. Liquid biopsy: The challenges of a revolutionary approach in oncology[J]. Int J Mol Sci, 2025, 26(11):5013.doi:10.3390/ijms26115013.
[57]	Sheriff S, Saba M, Patel R, et al. A scoping review of factors influencing the implementation of liquid biopsy for cancer care[J]. J Exp Clin Cancer Res, 2025, 44(1):50.doi:10.1186/s13046-025-03322-w. pmid: 39934875

检测技术	最低检测限	核心检测范围	最低cfDNA 需求量	实验室间一致性	核心临床应用场景	主要优势	主要局限性
ddPCR	0.01% VAF	预设热点突变、融合基因	1~5 ng	95% (VAF<0.5%)	MRD监测、疗效动态监测、已知靶点随访	敏感度高、重复性好、成本低、检测周期短	仅能检测已知位点,无法发现新发基因组变异
杂交捕获靶向 NGS	0.1% VAF	单核苷酸变异、InDel、CNA、融合基因、结构变异	≥20 ng	78% (VAF<0.5%)	初诊基因分型、耐药机制解析、克隆演化监测	可全景分析肿瘤基因组,发现新发驱动变异	对样本量要求高,成本较高,生物信息分析流程复杂
低深度全基因组测序	10% CNA阈值	全基因组CNA	5~10 ng	85%~90%	初诊拷贝数谱分析、组织样本不足时的替代分型	样本需求量低,可全基因组CNA分析	无法检测点突变与融合基因,对低肿瘤分数样本敏感度低

检测技术	最低检测限	核心检测范围	最低cfDNA 需求量	实验室间一致性	核心临床应用场景	主要优势	主要局限性
ddPCR	0.01% VAF	预设热点突变、融合基因	1~5 ng	95% (VAF<0.5%)	MRD监测、疗效动态监测、已知靶点随访	敏感度高、重复性好、成本低、检测周期短	仅能检测已知位点,无法发现新发基因组变异
杂交捕获靶向 NGS	0.1% VAF	单核苷酸变异、InDel、CNA、融合基因、结构变异	≥20 ng	78% (VAF<0.5%)	初诊基因分型、耐药机制解析、克隆演化监测	可全景分析肿瘤基因组,发现新发驱动变异	对样本量要求高,成本较高,生物信息分析流程复杂
低深度全基因组测序	10% CNA阈值	全基因组CNA	5~10 ng	85%~90%	初诊拷贝数谱分析、组织样本不足时的替代分型	样本需求量低,可全基因组CNA分析	无法检测点突变与融合基因,对低肿瘤分数样本敏感度低

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 2

References 57

Related Articles 8

Recommended Articles

Metrics

Comments

[1]	Wang Zhuangzhuang, Ren Huan, Liu Yanting, Tian Chunlei, Ai Wenbing. Construction of a nomogram to predict the risk of lung metastasis in extremity osteosarcomas based on the SEER database and its validation [J]. Clinical Focus, 2024, 39(5): 413-419.
[2]	. [J]. CLINICAL FOCUS, 2013, 28(3): 332-0.
[3]	. [J]. Clinical Focus, 2012, 27(17): 1535-1537.
[4]	. [J]. Clinical Focus, 2012, 27(16): 1470-0.
[5]	. [J]. CLINICAL FOCUS, 2011, 26(1): 66-67.
[6]	. [J]. CLINICAL FOCUS, 2010, 25(10): 900-900.
[7]	. [J]. CLINICAL FOCUS, 2008, 23(12): 899-900.
[8]	. [J]. CLINICAL FOCUS, 2005, 20(17): 1002-1003.