Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma

J Bone Oncol. 2020 Oct 21:26:100331. doi: 10.1016/j.jbo.2020.100331. eCollection 2021 Feb.

Abstract

Introduction: Osteosarcoma is a high-morbidity bone cancer with an unsatisfactory prognosis. The aim of this study is to develop novel potential prognostic biomarkers and construct a prognostic risk prediction model for recurrence in osteosarcoma.

Methods: By analyzing microarray data, univariate and multivariate Cox regression analyses were performed to screen prognostic RNA signatures and to build a prognostic model. The RNA signatures were validated using Kaplan-Meier curves. Then, we developed and validated a nomogram combining age, recurrence, metastatic, and Prognostic score (PS) models to predict the individual's overall survival at the 3- and 5-year points. Pathway enrichment of RNA was conducted based on the significant co-expressed RNAs.

Results: A total of 319 mRNAs and 14 lncRNAs were identified in the microarray data. One lncRNA (LINC00957) and six mRNAs (METL1, CA9, B3GALT4, ALDH1A1, LAMB3, and ITGB4) were identified as RNA signatures and showed good performances in survival prediction for both the training and validation cohorts. Cox regression analysis showed that the seven RNA signatures could independently predict overall survival. Furthermore, age, recurrence, metastatic, and PS models were identified as independent prognostic factors via univariate and multivariate Cox analyses (P < 0.05) and included in the prognostic nomogram. The C-index values for the 3- and 5-year overall survival predictions of the nomogram were 0.809 and 0.740, respectively.

Conclusions: The current study provides the novel potential of seven RNA candidates as prognostic biomarkers. Nomograms were constructed to provide accurate and individualized survival prediction for recurrence in osteosarcoma patients.

Keywords: LncRNA; Osteosarcoma; Prognostic signature; Recurrence; mRNA.