Prognostic model of osteosarcoma and to predict immune microenvironment based on genes related with neutrophil extracellular traps
HUANG Da-shuai
QI Yu-jiao
LI Dong-dong
LI Song-kai
Abstract：Objective Osteosarcoma is a primary malignant tumor commonly found in children and young adults.The 5-year survival rate of osteosarcoma patients has not substantially improved over the past 35 years,highlighting the need for further research to improve treatment outcomes.This study aims to investigate the role of neutrophil extracellular traps(NETs)in the occurrence and progression of osteosarcoma,providing guidance and treatment strategies for clinical therapy to improve patient prognosis.Methods The clinical data and corresponding RNA data of osteosarcoma patients were downloaded from the GEO database,and a consensus clustering was performed to identify new molecular subgroups.The ESTIMATE,MCPCounter,and ssGSEA analysis methods were used to determine the tumor immune microenvironment(TIME)and immune status of the identified molecular subgroups.To elucidate potential mechanisms,functional analysis methods such as GO,KEGG,and GSEA were employed.Lastly,a prognostic risk model was established using the LASSO algorithm and multivariate Cox regression analysis.Results This study demonstrated significant differences in survival rate between the two molecular subgroups(P=7.9e-3).The subgroup with better prognosis was associated with high immune scores,low tumor purity,high abundance of immune-infiltrating cells,and relatively higher immune status.GO and KEGG analyses showed that differentially expressed genes(DEGs)between the two subgroups were mainly enriched in immune-related and bone mineralization-related pathways.GSEA analysis further suggested that NETs may alter the immune microenvironment.Moreover,a risk model based on NETs-related genes could be used for risk stratification of osteosarcoma patients.Finally,a nomogram combining the risk model and clinical characteristics accurately predicted the prognosis of osteosarcoma patients.Conclusions The expressions of NETs-related genes in osteosarcoma patients are closely associated with the immune microenvironment,which can aid to accurately predict the prognosis of osteosarcoma.This finding provides important evidence to better understand the immune microenvironment and NETs regulatory mechanism in osteosarcoma,and opens up new avenues for future targeted therapies.
Keywords：OsteosarcomaMolecular targeted therapyModelsprognosisNeutrophiImmune microenvironment
Publication Date：2025-02-18
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：10( 155-164 )