Osteosarcoma (OS) is the most common malignant bone tumor in pediatrics. Despite the use of surgery and chemotherapy, the survival rate of patients who develop a metastatic disease or a poor response towards the chemotherapy remains dismal. Identification of novel biomarkers for early prognostication will facilitate risk-based stratification before the treatment is initiated, so that the high-risk patients can be treated more appropriately to increase their chance of survival. Others and we have previously reported that cytokines and chemokines were implicated in OS. In this study, we employed highly sensitive Luminex beads assays to investigate 90 cytokines/chemokines and receptors on a cohort of 40 OS plasma samples collected at diagnosis from the Texas Children's Hospital. The protein expression data were analysed to identify candidate biomarkers that correlate with the chemotherapy response, initial metastatic status, and overall survival. Then, the candidates were validated in a large set of 250 serum samples obtained from the Children's Oncology Group. Our results show that a three-protein signature consisting of CXCL9, CXCL10 and CXCL11, all ligands of the CXCR3 receptor, is significantly associated with survival. Interestingly, the CXCR3-axis has been previously implicated in an OS mouse model, but its role in human is still not known. Hence, the next step is to validate these prognostic biomarkers in an independent cohort of OS patient samples. In addition, we will test the expression of these molecules and their receptor in tumor samples to identify potential therapeutic targets. In summary, we characterized the expression of circulating cytokines/chemokines in osteosarcoma samples and identified candidate prognostic biomarkers that are linked to the CXCR3-axis. A further study of these molecules may allow us to develop a biomarker approach for early prognostication and a novel therapeutic approach for treating high-risk OS.

Citation Format: Ricardo J. Flores, Yiting Li, Aaron Kelly, Ching Lau, Tsz-Kwon Man. A three-protein cytokine signature that correlates with the prognosis of osteosarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2869. doi:10.1158/1538-7445.AM2014-2869