Pseudogene pair-based prognostic model reveals LAT as a biomarker of immune response in head and neck squamous cell carcinoma.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) often exhibit only partial responses to immunotherapy, resulting in poor prognosis and potential overtreatment. While pseudogenes are known to significantly impact the tumor microenvironment (TME) and tumor prognosis, their specific role in HNSCC remains unclear. METHODS: A prognostic risk profile for HNSCC patients was developed and validated using pseudogene pairs. The prognostic value of the risk signiture was assessed using survival analysis, ROC analysis, and Cox regression models. Correlations between our risk profile and immunologic characteristics of the TME were analyzed, with TIDE scores used to predict immunotherapy responses. LAT, identified as a central gene in the risk model through WGCNA and Friend analysis, was further investigated. LAT expression and its association with immune cells and immune checkpoints within the TME were examined using an internal cohort and immunofluorescence. RESULTS: The model based on pseudogene pairs demonstrated strong prognostic power, with significantly longer overall survival in low-risk patients compared to high-risk ones. Additionally, risk scores were inversely related to immune infiltration and predictive of immunotherapy response. LAT, identified as a potential hub gene in the low-risk group, showed stable performance across multiple validation sets and was positively correlated with T cell infiltration and high expression in an inflammatory TME. CONCLUSION: A pseudogene pair-based survival prediction model for HNSCC was developed and validated, providing valuable insights for HNSCC treatment. LAT may serve as a novel biomarker for predicting immune response.