Integrated bioinformatic analysis identifies distinct neddylation-associated proteasome genes and immune-related features in laryngeal squamous cell carcinoma

Neddylation contributes to cancer progression, but its relationship with proteasome-related genes and the immune microenvironment in laryngeal squamous cell carcinoma (LSCC) remains unclear. We aimed to identify neddylation-associated genes in LSCC and characterize their molecular, metabolic, and immune features. Transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed using differential expression, functional enrichment, and machine-learning approaches. Key genes were further evaluated by survival, pathway, immune infiltration, and somatic mutation analyses and validated by quantitative real-time PCR (qRT-PCR) in five paired LSCC and adjacent tissues. Seventy-four differentially expressed neddylation-related genes were identified. Four genes, KCTD6, PSMB2, PSMB4, and PSMD2, were selected by both LASSO and SVM-RFE. KCTD6-associated genes were enriched in bile acid metabolism, while macrophage M0 and resting CD4 + memory T cells were associated with prognosis. Lower PSMB4 and PSMD2 expression was associated with immune escape-related features. qRT-PCR in five paired specimens confirmed the predicted direction of expression change for all four genes (KCTD6 lower, and PSMB2, PSMB4, and PSMD2 higher in tumor); given the small paired sample, this provides directional confirmation only and does not establish biomarker performance. We identified a distinct set of proteasome-related neddylation-associated genes associated with metabolic and immune characteristics in LSCC. These findings suggest potential links between neddylation-associated proteasome genes and the immune microenvironment in LSCC.