Abstract
BACKGROUND: The understanding of the complex biological scenario of osteosarcoma will open the way to identifying new strategies for its treatment. Oxidative stress is a cancer-related biological scenario. At present, it is not clear the oxidative stress genes in affecting the prognosis and progression of osteosarcoma, the underlying mechanism as well as their impact on the classification of osteosarcoma subtypes. METHODS: We selected samples and sequencing data from TARGET data set and GSE21257 data set, and downloaded oxidative stress related-genes (OSRGs) from MsigDB. Univariate Cox analysis of OSRG was conducted using TARGET data, and the prognostic OSRG was screened to conduct unsupervised clustering analysis to identify the molecular subtypes of osteosarcoma. Through least absolute shrinkage and selection operator (LASSO) regression analysis and COX regression analysis of differentially expressed genes (DEGs) between subgroups, a risk assessment system for osteosarcoma was developed. RESULTS: 45 prognosis-related OSRGs genes were acquired, and two molecular subtypes of osteosarcoma were clustered. C2 cluster displayed prolonged overall survival (OS) accompanied with high degree of immune infiltration and enriched immune pathways. While cell cycle related pathways were enriched in C2 cluster. Based on DEGs between subgroups and Lasso analysis, 5 hub genes (ZYX, GJA5, GAL, GRAMD1B, and CKMT2) were screened to establish a robust prognostic risk model independent of clinicopathological features. High-risk group had more patients with cancer metastasis and death as well as C1 subtype with poor prognosis. Low-risk group exhibited favorable OS and high immune infiltration status. Additionally, the risk assessment system was optimized by building decision tree and nomogram. CONCLUSIONS: This study defined two molecular subtypes of osteosarcoma with different prognosis and tumor immune microenvironment status based on the expression of OSRGs, and provided a new risk assessment system for the prognosis of osteosarcoma.