Construction and validation model of necroptosis-related gene signature associates with immunity for osteosarcoma patients

Abstract

AbstractOsteosarcoma is the most common malignant tumor in children and adolescents and its diagnosis and treatment still need to be improved. Necroptosis has been associated with many malignancies, but its significance in diagnosing and treating osteosarcoma remains unclear. The objective is to establish a predictive model of necroptosis-related genes (NRGs) in osteosarcoma for evaluating the tumor microenvironment and new targets for immunotherapy. In this study, we download the osteosarcoma data from the TARGET and GEO websites and the average muscle tissue data from GTEx. NRGs were screened by Cox regression analysis. We constructed a prediction model through nonnegative matrix factorization (NMF) clustering and the least absolute shrinkage and selection operator (LASSO) algorithm and verified it with a validation cohort. Kaplan–Meier survival time, ROC curve, tumor invasion microenvironment and CIBERSORT were assessed. In addition, we establish nomograms for clinical indicators and verify them by calibration evaluation. The underlying mechanism was explored through the functional enrichment analysis. Eight NRGs were screened for predictive model modeling. NRGs prediction model through NMF clustering and LASSO algorithm was established. The survival, ROC and tumor microenvironment scores showed significant statistical differences among subgroups (P < 0.05). The validation model further verifies it. By nomogram and calibration, we found that metastasis and risk score were independent risk factors for the poor prognosis of osteosarcoma. GO and KEGG analyses demonstrate that the genes of osteosarcoma cluster in inflammatory, apoptotic and necroptosis signaling pathways. The significant role of the correlation between necroptosis and immunity in promoting osteosarcoma may provide a novel insight into detecting molecular mechanisms and targeted therapy.