Development and in vitro validation of a degradation-related gene-based prognostic model for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSC) exhibits significant heterogeneity and a high incidence rate, yet definitive prognostic markers remain unknown. Disruptions in cellular homeostasis due to degradation-related gene sets may trigger carcinogenic processes; however, the precise contributions of these genes to the onset and progression of HNSC are not fully elucidated. This study analyzed data from public databases to identify degradation-related genes (DRGs) associated with patient outcomes. A risk model was subsequently developed through weighted gene co-expression network analysis (WGCNA) and enrichment analysis. Six genes independently correlated with prognosis were identified, facilitating the construction of a nomogram that combined risk scores and clinical data. The mRNA levels of the model-related genes in HaCaT (a normal human keratinocyte cell line) and CAL27 (a human HNSC cell line) were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, functional assays including wound healing and EdU incorporation were conducted to explore the role of BCL2A1 in HNSC cells. Differences in responses to chemotherapy and immunotherapy among risk groups were evaluated. This study elucidates the role of degradation-related genes in HNSC by identifying predictive features of patient outcomes and exploring their clinical applicability. In vitro studies have confirmed that the expression levels of model genes (ZAP70, BCL2A1, APOC1, S1PR4) differ significantly between HaCaT and CAL27 cell lines, suggesting their potential involvement in HNSC prognosis. Additional functional assays revealed that silencing BCL2A1 markedly inhibits the migration and proliferation abilities of CAL27 cells. This study developed a prognostic model based on DRGs and systematically evaluated its clinical applicability, thereby providing a robust theoretical foundation for future prognostic prediction and therapeutic strategies in patients with HNSC.