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A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
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A novel prognostic model for osteosarcoma using circulating CXCL10 and FLT3LG
Ricardo J Flores1,2,3, Aaron J Kelly1,2,4, Yiting Li1,2
1Texas Children's Cancer and Hematology Centers, Texas Children's Hospital, Houston, Texas.
Cancer
|August 17, 2016
Summary
High circulating levels of C-X-C motif chemokine ligand 10 (CXCL10) and Fms-related tyrosine kinase 3 ligand (FLT3LG) indicate worse survival in pediatric osteosarcoma patients. These biomarkers, along with metastasis status, can stratify patients into distinct risk groups for tailored therapy.
Area of Science:
- Oncology
- Biomarker Discovery
- Pediatric Cancer Research
Background:
- Osteosarcoma (OS) is the most common pediatric bone malignancy.
- Early prognostication is crucial for risk-stratified treatment of OS.
- Identifying novel circulating biomarkers can improve patient outcomes.
Purpose of the Study:
- To investigate the prognostic significance of circulating cytokines and chemokines in osteosarcoma patients at initial diagnosis.
- To identify novel biomarkers for predicting overall survival and event-free survival in OS.
- To develop a multivariate model for risk stratification in osteosarcoma.
Main Methods:
- Luminex assays were used to measure cytokine/chemokine concentrations in discovery (n=37) and validation (n=233) OS cohorts.
- Biomarker validation was performed using blood samples from pediatric osteosarcoma patients.
- A multivariate model was constructed incorporating validated biomarkers and metastatic status.
Main Results:
- Circulating C-X-C motif chemokine ligand 10 (CXCL10), Fms-related tyrosine kinase 3 ligand (FLT3LG), interferon γ (IFNG), and C-C motif chemokine ligand 4 (CCL4) were associated with overall survival.
- CXCL10 and FLT3LG were independent prognostic factors, while CCL4 differentiated cancer cases from controls.
- A multivariate model combining CXCL10, FLT3LG, and metastatic status stratified patients into 4 risk groups with distinct survival outcomes (P = 1.6 × 10-8).
Conclusions:
- Elevated circulating CXCL10 and FLT3LG levels predict poorer survival in osteosarcoma.
- These biomarkers offer potential for novel risk-based stratification and targeted therapies in OS.
- Further research into CXCL10 and FLT3LG pathways may lead to improved osteosarcoma treatment strategies.
