The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma.

Abstract

Osteosarcoma (OS) is the most common pediatric bone cancer. Despite advances in treatment regimens, the survival rate remains 60-70%. There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. Our laboratory has previously identified that circulating serum amyloid A (SAA) and CXC chemokine ligand 4 (CXCL4) are upregulated in patients with OS. In this study, we tested if they could be used as prognostic biomarkers. We used enzyme-linked immunosorbent assays to measure their concentrations in serum samples (n = 233) and immunohistochemistry to examine their expressions in primary tumors (n = 37). Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. Patients with "high SAA" and "low CXCL4" circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, P = 0.014), which was independent of the metastatic status. These patients also exhibited a significantly higher rate of poor histologic response to chemotherapy. Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, P = 0.005). Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in OS. Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in OS.