Identification of a 7-mRNA signature as a prognostic biomarker in pediatric osteosarcoma.

Abstract

BackgroundThe aim of the present study was to establish a prognostic model for the survival of children with osteosarcoma (OS).MethodsThe mRNA expression and clinical characteristics of pediatric patients with OS were extracted from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. After genes with differential mRNA expression were identified, univariate and multivariate Cox analyses were performed, and a prognostic model of pediatric OS was established. The prognostic values of a 7-mRNA signature were evaluated using the receiver-operating characteristic (ROC) curve in pediatric patients with OS.ResultsA total of 19,496 differentially expressed mRNAs were identified, including 267 upregulated mRNAs and 104 downregulated mRNAs. After univariate and multivariate Cox analyses, seven mRNA species (SCGB3A1, MUC17, ADH1B, KRT83, RP1-37E16.12, FIGF, and SFTPD) were found to be closely associated with survival. These mRNA species were mainly enriched in glycolysis/gluconeogenesis, arachidonic acid metabolism, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, tight junction, and complement and coagulation cascade pathways. A predictive model using the sum of independent prognostic values of the seven mRNA species as the risk score was proposed. The risk score was calculated as follows: risk score = 0.242257 × SCGB3A1 + 0.168999 × MUC17 + 0.415514 × ADH1B + 0.488864 × KRT83 + 0.360864 × RP1-37E16.12 – 0.2991 × FIGF – 0.39576 × SFTPD. Pediatric patients with OS were assigned to low- and high-risk groups based on the risk score. The ROC curve analysis showed that the 7-mRNA prediction model performed well [area under the curve (AUC): 0.858].ConclusionsA 7-mRNA signature has the potential to predict the prognosis of pediatric patients with OS, and therefore warrants further validation.