Abstract
Head and neck squamous cell carcinoma (HNSCC) has been characterized by a low therapeutic response and poor prognosis. Currently, there are no reliable predictive models for HNSCC progression and therapeutic efficacy. This study explores the role of diverse patterns of cell death in tumor development, positing them as predictive factors of HNSCC prognosis. We utilized bulk transcriptome and single-cell transcriptome, align with clinical information from TCGA and GEO database, to analyze genes associated with 15 types of cell death and construct a cell death index (CDI) signature. The associations of CDI with tumor-infiltrating immune cells and immunotherapy-related biomarkers were also evaluated using various algorithms. The CDI signature emerged as a robust prognosis biomarker that could identify patients who can benefit potentially from immunotherapy, thus improving diagnostic accuracy and optimizing clinical decisions in HNSCC management. Notably, we discovered that CAAP1 deficiency not only induced apoptosis but also enhanced anti-tumor immunity, suggesting its potential as a target for clinical drug development.