Identification and characterization of mitochondrial autophagy-related genes in osteosarcoma and predicting clinical prognosis

Abstract

Background Osteosarcoma (OS), with its poor prognosis and risk of metastasis, is the most common primary solid malignant bone tumor. Mitochondrial autophagy has been shown to prevent cancer. Therefore, the aim of this study was to investigate the prognostic genes associated with mitochondrial autophagy in OS. Methods The OS related dataset, TARGET-OS, GSE99671 and GSE21257 were downloaded from public database. The differential expression genes (DEGs1) were obtained between OS and normal samples in GSE99671. The single-sample Gene Set Enrichment Analysis (ssGSEA) was used to calculate the scores of 29 mitochondrial autophagy related genes (MARGs) in OS samples, and the samples in TARGET-OS were divided into high-/low-rating groups, so as to obtain the DEGs2 between the two groups. Then the DEGs1 were intersected with DEGs2 to obtain mitochondrial autophagy-related differential genes (MDGs). Subsequently, prognostic genes were screened through multiple steps and risk score was calculated. TARGET-OS was divided into high and low risk groups according to the best cutoff value of risk score. Then, GSEA was performed in two risk groups. Furthermore, the correlation between immune microenvironment and prognostic genes was evaluated. Results In all 31 MDGs were obtained via overlap of 3,207 DEGs1 and 622 DEGs2. Then, 5 prognostic genes were screened via multi-step regression analysis, namely KLK2, NRXN1, HES5, OR2W3 and HS3ST4. Kaplan-Meier (K-M) curve showed patients in the high-risk group had shorter survival time and lower survival rate. Further, GSEA results suggested that two risk group were enriched into abc transporter and glycolysis glucose production. Immunoanalysis found that 11 immune cells and 3 immune functions were remarkably different between two groups, such as MDSC and Type 1 T helper cell. HS3ST4 had strongest positive correlation with macrophage, and NRXN1 had strongest negative correlation with memory B cell. The expressions of HAVCR2 and PDCD1LG2 were higher in the low-risk group. Dysfunction had remarkable difference between the two risk groups. Conclusion In this study, five prognostic genes associated with mitochondrial 1autophagy were identified and a risk model was constructed, providing a new idea for the diagnosis and treatment of OS.