Identification of a novel autophagy-related gene signature for predicting metastasis and survival in patients with osteosarcoma

Abstract

Background: Osteosarcoma (OS) is a bone malignant tumor that occurs in children and adolescents. Due to a lack of reliable prognostic biomarkers, the prognosis of OS patients is often uncertain. This study aimed to construct an autophagy-related gene signature to predict the prognosis of OS patients.Methods: The gene expression profile data of OS and normal muscle tissue samples were downloaded separately from the Therapeutically Applied Research To Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases . The differentially expressed autophagy-related genes (DEARGs) in OS and normal muscle tissue samples were screened using R software, before being subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A protein-protein interaction (PPI) network was constructed and hub autophagy-related genes were screened. Finally, the screened autophagy-related genes were subjected to univariate Cox regression, Lasso Cox regression, survival analysis, and clinical correlation analysis.Results: A total of 120 DEARGs and 10 hub autophagy-related genes were obtained. A prognostic autophagy-related gene signature consisting of 9 genes ( BNIP3 , MYC , BAG1 , CALCOCO2 , ATF4 , AMBRA1 , EGFR , MAPK1 , and PEX ) was constructed. This signature was significantly correlated to the prognosis ( P <0.0001) and distant metastasis of OS patients ( P = 0.013).Conclusion: This signature based on 9 autophagy-related genes could predict metastasis and survival in patients with OS.

Determinants and impact of diagnostic interval in bone sarcomas: A retrospective cohort study

“…24,25 In fact, the presence of metastases at the time of diagnosis has paradoxically been reported to be associated with shorter diagnostic intervals by Bacci et al 26 This reflects the presence of a gene expression profile at baseline in bone sarcomas that predicts subsequent metastatic disease progression. 27 Interestingly, the social factors of place of residence and distance from the treating centre were not found to be associated with diagnostic interval. This could be explained by the fact that there is likely a general lack of awareness in cancer diagnostics and management even in urban centres in resource-challenged settings.…”

“…In fact, the presence of metastases at the time of diagnosis has paradoxically been reported to be associated with shorter diagnostic intervals by Bacci et al 26 . This reflects the presence of a gene expression profile at baseline in bone sarcomas that predicts subsequent metastatic disease progression 27 …”