Prognostic and clinicopathological significance of circulating tumor cells in osteosarcoma
Open accessAbstract
Osteosarcoma is the most common form of primary malignant bone tumor, with metastasis playing an essential role in determining a patient's prospects for survival. It is essential that new and better molecular targets that respond effectively to therapies and are predictive of the risk of tumor metastasis are identified. We have therefore undertaken the present prospective study to ascertain the clinical significance of circulating tumor cells (CTCs) in osteosarcoma patients. Peripheral blood was obtained from patients both pre- and post-surgery then processed using a CanPatrol™ system, an enrichment technique allowing isolation of CTCs by virtue of their size at baseline. Multiplex RNA in situ hybridization (RNA-ISH) was subsequently conducted to characterize the CTCs based on various molecular markers including MTA1, CD45, EpCAM, CK8, CK19, Vimentin and Twist. MTA1 expression was further validated by immunohistochemistry of the tumor tissue. Besides defining a diagnosis and prognosis for osteosarcoma patients, the correlation between CTC count and their molecular and clinicopathological characteristics was found to assist in the analysis of the response of patients to neoadjuvant chemotherapy. Our results revealed that the number of CTCs was significantly higher at baseline in metastatic patients than in those whose osteosarcomas were localized. The variation was attributed to the neoadjuvant chemotherapy treatment. A cut-off value of 7 CTCs/5 mL was found to effectively distinguish patients who had either a favorable or unfavorable prognosis. Notably, the ratio of mesenchymal CTCs at baseline was found to be higher in metastatic vs. localized osteosarcoma patients. In addition, the expression of MTA1 was higher in mesenchymal CTCs than the other CTC phenotypes. Furthermore, immunohistochemical analysis demonstrated a higher expression of MTA1 in tumor tissues from metastatic osteosarcoma patients. Taken together, our findings conclusively establish that the number and molecular phenotype of CTCs are predictive of tumor metastasis and the response of patients to neoadjuvant chemotherapy.
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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 [25]
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 [25]
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 [25]
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 [25]
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 [25]
Another osteosarcoma study detected baseline CTCs in 28 of 30 patients, with a median of 6 CTCs per 5 mL of blood.
“Another osteosarcoma study detected baseline CTCs in 28 of 30 patients, with a median of 6 CTCs per 5 mL of blood [ 25 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [25]
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- Authors
- Li, M., Lu, Y., Long, Z., Li, M., Kong, J., Chen, G., & Wang, Z.
- Affiliations
- Xijing Hospital (CN)
- Corresponding author
- Li, Minghui
- Venue
- Journal of Bone Oncology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 16
- Pages
- 100236
- ISSN
- 2212-1366 (ISSN-L)
- 2212-1374
- PMC
- PMC6475710
- OpenAlex
- W2930896415
- Cited by
- 27
- References
- 48
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 2 · 2020: 2
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of bone oncology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fourth Military Medical University
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Keywords
- osteosarcoma, circulating tumor cells, metastasis, prognostic factors, neoadjuvant chemotherapy response, MTA1, mesenchymal CTCs
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