Abstract

In this study, we identified eight survival-related metabolic genes in differentially expressed metabolic genes by univariate Cox regression analysis based on the therapeutically applicable research to generate effective treatments (n = 84) data set and genotype tissue expression data set (n = 396). We also constructed a six metabolic gene signature to predict the overall survival of osteosarcoma (OS) patients using least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Our results show that the six metabolic gene signature showed good performance in predicting survival of OS patients and was also an independent prognostic factor. Stratified correlation analysis showed that the metabolic gene signature accurately predicted survival outcomes in high-risk and low-risk OS patients. The six metabolic gene signature was also verified to perform well in predicting survival of OS patients in an independent cohort (GSE21257). Then, using univariate Cox regression and Lasso Cox regression analyses, we identified an eight metabolism-related long noncoding RNA (lncRNA) signature that accurately predicts overall survival of OS patients. Gene set variation analysis showed that the apical surface and bile acid metabolism, epithelial mesenchymal transition, and P53 pathway were activated in the high-risk group based on the eight metabolism-related lncRNA signature. Furthermore, we constructed a competing endogenous RNA (ceRNA) network and conducted immunization score analysis based on the eight metabolism-related lncRNA signature. These results showed that the six metabolic gene signature and eight metabolism-related lncRNA signature have good performance in predicting the survival outcomes of OS patients.

Highlights

  • Osteosarcoma (OS) is a primary malignant bone cancer and commonly occurs in adolescents and children

  • Our results suggest that the six metabolic gene signature and eight metabolism-related long noncoding RNA (lncRNA) signature identified show robust performance in predicting the survival outcomes of OS patients

  • Eight metabolic genes were found to be significantly correlated with OS based on univariate Cox regression analysis

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Summary

Introduction

Osteosarcoma (OS) is a primary malignant bone cancer and commonly occurs in adolescents and children. The overall annual incidence of OS is 3.4 million worldwide (Mirabello et al, 2009; Pingping et al, 2019; Czarnecka et al, 2020; Mirabello et al, 2020). OS typically occurs in the metaphysis of the long bones, such as the distal femur (43%), proximal tibia. Metabolic Genes and Metabolism-Related lncRNAs (23%), or humerus (10%) (Isakoff et al, 2015). Previous reports suggest that the 5-year survival rate of patients with nonmetastatic OS is 70–75%, but the long-term survival rate of metastatic OS patients is only 30% (Anwar et al, 2020). There is an urgent need to identify novel targets and biomarkers for the diagnosis and prognosis of OS to improve the survival rate of OS patients

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