Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis
Open accessAbstract
OBJECTIVE: Osteosarcoma (OS) is an aggressive, highly metastatic, relatively drug-resistant bone tumor with poor long-term survival rates. The presence and persistence of circulating tumor cells (CTCs) in the peripheral blood are believed to be associated with treatment inefficiency and distant metastases. A blood-based CTC test is thus greatly needed for monitoring disease progression and predicting clinical outcomes. However, traditional methods cannot detect CTCs from tumors of mesenchymal origin such as OS, and research on CTC detection in mesenchymal tumors has been hindered for years. METHODS: In this study, we developed a CTC test based on hexokinase 2, a metabolic function-associated marker, for the detection and surveillance of OS CTCs, and subsequently explored its clinical value. Twelve patients with OS were enrolled as the training cohort for serial CTC tests. Dynamic CTC counting, in combination with therapy evaluation and post-treatment follow-up, was used to establish a model for predicting post-chemotherapy evaluation and disease-free survival, and the model was further validated with a cohort of 8 patients with OS. RESULTS: Two dynamic CTC number patterns were identified, and the resulting predictive model exhibited 92% consistency with the clinical outcomes. This model suggested that a single CTC test has similar predictive power to serial CTC analysis. In the validation cohort, the single CTC test exhibited 100% and 87.5% consistency with therapy response and disease-free survival, respectively. CONCLUSIONS: Our non-invasive test for detection and surveillance of CTCs enables accurate prediction of therapy efficiency and prognosis, and may be clinically valuable for avoiding inefficient therapy and prolonging survival.
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In osteosarcoma, CTC burden, phenotype, and dynamic changes have been associated with metastatic disease, treatment response, and prognosis.
“In osteosarcoma, CTC burden, phenotype, and dynamic changes have been associated with metastatic disease, treatment response, and prognosis [ 25 , 26 , 27 , 28 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [28]
Broad plasma panels, CNA-based WGS, methylation-based assays, cfRNA approaches, and CTC-based strategies remain more exploratory or proof-of-concept in most sarcoma subtypes, particularly when applied to low-volume MRD or routine surveillance settings.
“In contrast, broad plasma panels, CNA-based WGS, methylation-based assays, cfRNA approaches, and CTC-based strategies remain more exploratory or proof-of-concept in most sarcoma subtypes, particularly when applied to low-volume MRD or routine surveillance settings [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [28]
The broader application of CTC-based methods across soft-tissue sarcomas remains limited by platform heterogeneity and uncertain prevalence.
“CTC-based methods provide complementary biological information, particularly in osteosarcoma, but their broader application across soft-tissue sarcomas remains limited by platform heterogeneity and uncertain prevalence [ 25 , 26 , 27 , 28 , 29 , 39 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [28]
CTC detection is technically difficult in mesenchymal tumors, especially when platforms rely on epithelial markers such as EpCAM or cytokeratins.
“However, CTC detection is technically difficult in mesenchymal tumors, especially when platforms rely on epithelial markers such as EpCAM or cytokeratins.”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [28]
CTC-based methods provide complementary biological information, particularly in osteosarcoma.
“CTC-based methods provide complementary biological information, particularly in osteosarcoma, but their broader application across soft-tissue sarcomas remains limited by platform heterogeneity and uncertain prevalence [ 25 , 26 , 27 , 28 , 29 , 39 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [28]
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- Authors
- Mu, H., Zuo, D., Chen, J., Liu, Z., Wang, Z., Yang, L., Shi, Q., & Hua, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Shi, Qihui
- Hua, Yingqi
- Venue
- Cancer Biology & Medicine
- Publisher
- China Anti-cancer Association
- Published
- 2022-09-23
- Volume
- 19
- Issue
- 9
- Pages
- 1397-1409
- ISSN
- 2095-3941 (ISSN-L)
- PMC
- PMC9500224
- OpenAlex
- W4298087450
- Cited by
- 23
- References
- 26
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 2 · 2022: 1
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cancer Biology and Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Shanghai Jiao Tong University
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- osteosarcoma, circulating tumor cells, hexokinase 2, CTC detection, liquid biopsy, chemotherapy response prediction, disease-free survival, mesenchymal tumors, prognostic model
- MeSH terms
- Bone Neoplasms, Hexokinase, Humans, Neoplastic Cells, Circulating, Prognosis, Osteosarcoma, Biomarkers, Tumor
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