Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma
Open accessAbstract
Background: Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. Methods: We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol ® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 ( IMP3 ) expression in CTCs were analyzed. Results: CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients ( P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features ( P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively ( P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3 -positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. Conclusion: This study demonstrates that the CTCs, especially the IMP3 -positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.
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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 [26]
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 [26]
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 [26]
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 [26]
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 [26]
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- Authors
- Dai, S., Shao, X., Wei, Q., Du, S., Hou, C., Li, H., & Jin, D.
- Affiliations
- Third Affiliated Hospital of Southern Medical University (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Corresponding author
- Li, Haomiao
- Jin, Dadi
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2023-02-23
- Volume
- 13
- Pages
- 819357-819357
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC10021108
- OpenAlex
- W4321598048
- Cited by
- 20
- References
- 49
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 1
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Science and Technology Planning Project of Guangdong Province
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- osteosarcoma, circulating tumor cells, IGF2BP3, metastasis, prognostic factors, liquid biopsy, Enneking stage, disease progression monitoring, RNA in situ hybridization, disease-free survival, overall survival, recurrence-free survival
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