SYSTEMS BIOLOGY SIGNATURE FOR PROGNOSIS OF NON-OSSIFYING FIBROMA

Abstract

Introduction: Non-ossifying fibroma (NOF) is a frequent fibrotic lesion of bone, observed in up to 40% of children. Extensive NOF lesions and deficient healing may cause a pathological fracture or a malignant transformation. Prediction of complications requires knowledge of the mechanisms controlling NOF, and systemic analysis may provide insight into these mechanisms. Aim: To identify regulators that may predict the risk of complications, e.g., pathologic fracture or malignant transformation. Methods: Data were retrieved from public databases, e.g., PubMed and dedicated databases. We retrieved regulators with confirmed association with NOF, regulators of processes engaged in NOF, and regulators of bone remodelling and giant cell tumors of bone. Systemic analysis was performed using Cytoscape and FunCoup tools. Results: Networks representing NOF mechanisms, bone healing, and malignant transformation were generated. The network analysis identified mechanisms that may predict the efficacy of healing of NOF lesion or the risk of malignant transformation of NOF. Forty-one compounds were identified as potential signature predictor of the efficacy of bone healing. The list contains known and novel regulators of bone. Signalling pathways, hormones, vitamins, minerals, proliferation and differentiation regulators are in the 41 signature. We report here a list of 62 molecules that are engaged in bone tumorigenesis and in NOF, e.g., oncogenes and tumor suppressors, tumorigenesis-associated signalling pathways and hormones Deregulation of these molecules increases the risk of malignant transformation of NOF. Conclusion: The 41 and 62 signatures identify potential markers of the risk of non-efficient healing or malignant transformation of NOF.