Prognostic Value of Neutrophil Extracellular Trap-Related Molecular Signatures in Immune-Related Genes for Patients with Osteosarcoma

DOI: https://doi.org/10.62517/jmhs.202605126

Author(s)

Wenjin Jiang1,2,#, Wei Zheng3,#, Xinxi Cai4, Jingpeng Wu4, Jin Li4, Sunyu Chen1,*

Affiliation(s)

1Orthopedic department, Fuzhou Second General Hospital, Fuzhou, Fujian, China 2Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopaedic Trauma (2020Y2014), Fuzhou, Fujian, China 3Orthopedic department, Lianjiang County General Hospital, Fuzhou, Fujian, China 4Fujian University of Traditional Chinese Medic, Fuzhou, Fujian, China ※These authors have contributed equally to this work *Corresponding Author

Abstract

This study investigated the prognostic value of neutrophil extracellular trap (NET)-related molecular signatures in immune-related genes for osteosarcoma patients, as well as their potential to provide molecular targets for individualized therapeutic strategies. Osteosarcoma patients’ gene expression profiles and clinical follow-up data were retrieved from the TARGET database as the training set and the GEO database (GSE21257) as the external validation set. Consensus clustering was performed for molecular subtyping based on NET-related gene (NRG) expression patterns, and bioinformatic analyses were applied to compare biological functions, tumor microenvironment and immune infiltration characteristics across subtypes. LASSO regression was used to screen core prognostic NRGs and construct a prognostic signature, whose predictive efficacy was validated via multiple statistical methods, and a clinical nomogram was further constructed by integrating the signature’s risk score with clinical characteristics. The results showed that patients could be stratified into two molecular subtypes with distinct prognostic and immune-related features, and the constructed NRG-based signature effectively divided patients into high- and low-risk groups with different prognosis, acting as an independent risk factor for poor prognosis in osteosarcoma and outperforming previously published prognostic signatures. The combined nomogram improved prognosis prediction accuracy, and high risk scores were associated with osteosarcoma distant metastasis. In conclusion, NRG expression characteristics are closely correlated with osteosarcoma prognosis and tumor immune microenvironment, and the core NRG-based prognostic signature can serve as a novel molecular biomarker, providing new insights for osteosarcoma risk stratification and precise immunotherapy.

Keywords

Osteosarcoma; Neutrophil Extracellular Traps; Immune-Related Genes; Prognostic Signature; Tumor Immune Microenvironment; Risk Stratification

References

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