Identification of prognostic neutrophil extracellular traps-related genes subtypes predicts prognostic and immune microenvironment for osteosarcoma patients

Abstract

Background Neutrophil extracellular traps (NETs) are known to play a crucial role in tumorigenesis. The present study sought to identify a molecular subtype and prognostic signature that is based on NETs-related genes (NRGs). NRGs may provide insight into osteosarcoma molecular mechanisms and predict prognosis. Methods We search TARGET and GEO databases to obtain expression levels of NRGs and clinical data of 89 patients with osteosarcoma. Consensus clustering analysis was used to explore the molecular subtypes. The differences (variations) in immune characteristics and biological processes across various molecular subtypes were examined using GSEA, ESTIMATE, and ssGSEA. An NRG signature was constructed using LASSO regression. Kaplan-Meier (K-M) plots, Cox regressions, and nomogram analysis were performed to determine its prognostic significance in osteosarcoma. Results Molecular subtypes associated with NETs were discovered. Cluster 2 was linked to a more favorable prognosis, greater immune cell infiltration degree and immunogenicity, and a more favorable immunotherapy response than Cluster 1. Patients in the low-risk group had better survival outcomes than patients in the high-risk group. Additionally, high risk scores were independently correlated with poor prognoses as per the Cox regression analysis. Furthermore, the nomogram, which incorporates clinical characteristics and risk scores, has the potential to improve prediction accuracy. Conclusion Patients with osteosarcoma may be divided into two subtypes of NETs. An NRG-related prognostic signature was developed for patients with osteosarcoma.