Autophagy-Related Genes and Long Noncoding RNAs Signatures as Predictive Biomarkers for Osteosarcoma Survival

Front Cell Dev Biol. 2021 Aug 26:9:705291. doi: 10.3389/fcell.2021.705291. eCollection 2021.

Abstract

Osteosarcoma is a common malignant tumor that seriously threatens the lives of teenagers and children. Autophagy is an intracellular metabolic process mediated by autophagy-related genes (ARGs), which is known to be associated with the progression and drug resistance of osteosarcoma. In this study, RNA sequence data from TARGET and genotype-tissue expression (GTEx) databases were analyzed. A six autophagy-related long noncoding RNAs (ARLs) signature that accurately predicted the clinical outcomes of osteosarcoma patients was identified, and the relations between immune response and the ARLs prognostic signature were examined. In addition, we obtained 30 ARGs differentially expressed among osteosarcoma tissue and healthy tissue, and performed functional enrichment analysis on them. To screen for prognostic-related ARGs, univariate and LASSO Cox regression analyses were successively applied. Then, multivariate regression analysis was used to complete construction of the prognostic signature of ARGs. Based on the risk coefficient, we calculated the risk score and grouped the patients. Survival analysis showed that high-risk patients evolve with poor prognosis. And we verified the prognosis model in the GSE21257 cohort. Finally, verification was conducted by qRT-PCR and western blot to measure the expression of genes. The results show that autophagy-related marker models may provide a new therapeutic and diagnostic target for osteosarcoma.

Keywords: autophagy; biomarkers; lncRNA; osteosarcoma; prognostic signature.