Identification of Novel Neddylation‐Related Molecular Subtypes in Non‐Small Cell Lung Cancer With Implications for Prognosis and the Immune Landscape

ABSTRACT Lung cancer stands as the primary cause of fatalities contacted to cancer, with nonsmall cell lung cancer (NSCLC) comprising the bulk of these cases. Protein neddylation, a posttranslational alteration akin to ubiquitination. The study aims to identify neddylation‐related genes in NSCLC and to predict molecular models hold significant promise for forecasting the prognosis of NSCLC patients. Clinical information stemmed from the Cancer Genome Atlas (TCGA) database; neddylation‐related genes (NRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Patients were clustered into two subtypes utilizing the Kmeans method. These genes were then screened using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A nomogram was created to predict the prognosis of NSCLC. The model was validated in independent Gene Expression Omnibus (GEO) data sets: GSE30219. We performed extensive model validations to assess the prognostic significance of the signature. The immune landscape of risk groups was characterized using Single Sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms. Subsequently, we also performed drug sensitivity evaluation. Based on the expression profiles of 26 neddylation‐associated genes, we classified patients into two distinct subtypes, then identified ten neddylation‐related genes that serve as prognostic biomarkers. Receiver operating characteristic (ROC) curves noted that these neddylation‐related were effective in predicting patients prognosis. Furthermore, patients at high‐risk have poor survival rates. Besides, high‐risk group exhibited lower immune cell infiltration levels, displayed a marked divergence in the expression pattern of immune checkpoint molecules. Lastly, we identified potential drugs and evaluated the drug sensitivity for NSCLC. In conclusion, we constructed novel neddylation‐related molecular subtypes and revealed their immunological characteristics that may function as prognostic biomarkers for NSCLC patients.