Abstract
OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide with a poor prognosis. PANoptosis is a novel programmed cell death pathway. Presently, the expression pattern and prognosis of PANoptosis in HNSCC remain not fully elucidated. METHODS: The expression profile and corresponding clinical information were downloaded from The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO). Univariate cox regression and consensus clustering analysis were applied to identify PANoptosis-related molecular subtypes. The subtype specific pathways were identify through gene set variation analysis (GSVA). The differentially expressed genes (DEGs) between subtypes were identified using limma algorithm. Then, a PANoptosis-related signature was constructed using univariate cox regression analysis and lasso analysis based on the DEGs. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were exploited to evaluate the prognostic value of signature. In addition, the relationship between signature, immune microenvironment, and drug sensitivity was examined. RESULTS: A total of 707 tumor samples and 44 normal samples with corresponding clinical information were included in the study. Two molecular subtypes with distinct overall survival rates, immune cell infiltration and pathways were identified using clustering analysis. Compared to cluster N, cluster A was characterized by a favorable survival outcome and increasing immune cell infiltration. The TIDE analysis result indicated that patients in cluster A may have a better response to immunotherapy. In addition, a novel PANoptosis-related signature was constructed based on the DEGs from two clusters. The patients with high PANoptosis score were corresponding to a poor survival outcome. Cox regression analysis result revealed that the signature score could serve as an independent prognostic factors. Further drug analysis result suggest that patients in high PANoptosis group have more sensitivity to docetaxel drugs. CONCLUSIONS: The two molecular subtypes and PANoptosis-related signature have the potential to underlying the molecular mechanism and provide reliable marker for the prognosis of HNSCC.