Abstract
Purpose Osteosarcoma is the most common primary and highly invasive bone tumor in children and adolescents. The purpose of this study is to construct a multi-gene expression feature related to autophagy, which can be used to predict the prognosis of patients with osteosarcoma. Materials and methods. The clinical and gene expression data of patients with osteosarcoma were obtained from the target database. Enrichment analysis of autophagy-related genes related to overall survival (OS-related ARGs) screened by univariate Cox regression was used to determine OS-related ARGs function and signal pathway. In addition, the selected OS-related ARGs were incorporated into multivariate Cox regression to construct prognostic signature for the overall survival (OS) of osteosarcoma. Use the dataset obtained from the GEO database to verify the signature. Besides, gene set enrichment analysis (GSEA) were applied to further elucidate the molecular mechanisms. Finally, the nomogram is established by combining the risk signature with the clinical characteristics. Results Our study eventually included 85 patients. Survival analysis showed that patients with low riskScore had better OS. In addition, 16 genes were included in OS-related ARGs. We also generate a prognosis signature based on two OS-related ARGs. The signature can significantly divide patients into low-risk groups and high-risk groups, and has been verified in the data set of GEO. Subsequently, the riskScore, primary tumor site and metastasis status were identified as independent prognostic factors for OS and a nomogram were generated. The C-index of nomogram is 0.789 (95% CI: 0.703~0.875), ROC curve and calibration chart shows that nomogram has a good consistency between prediction and observation of patients. Conclusions ARGs was related to the prognosis of osteosarcoma and can be used as a biomarker of prognosis in patients with osteosarcoma. Nomogram can be used to predict OS of patients and improve treatment strategies.
Highlights
Osteosarcoma is the most common primary and highly invasive bone tumor, which originates from primitive mesenchymal cells and usually occurs in children and adolescents [1,2,3]
The demographic and clinicopathological statistics of the 85 samples are shown in Table 1,The clinical characteristics of 53 verification cohort samples obtained from the GSE21257 cohort are shown in Table S1.The classification of age is realized by the best cut-off value obtained by the X-tile software
We found that the results of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis are mostly related to autophagy
Summary
Osteosarcoma is the most common primary and highly invasive bone tumor, which originates from primitive mesenchymal cells and usually occurs in children and adolescents [1,2,3]. The 5-year survival rate of children and young people with non-metastatic osteosarcoma was 60%. For patients with metastasis or poor response to initial treatment, the 5-year survival rate was only 20% [6, 7]. A better understanding of the pathogenesis of osteosarcoma and identification of biomarkers that can predict the prognosis of osteosarcoma are essential for improving the prognosis of patients. There is BioMed Research International an urgent need for a more accurate quantitative prediction tool to assist clinical diagnosis and treatment
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