Prognostic Role Of Pyroptosis-related Gene Signature And Validation Of Hub Gene In Head And Neck Squamous Cell Carcinoma

Objective:1.A prognostic model was developed based on pyroptosis-related genes(PRGs)to provide prognostic value for patients with head and neck squamous cell carcinoma(HNSCC).2.Hub genes were screened and their expression significance in HNSCC was explored.Methods:1.The m RNA expression and clinical data of 33 PRGs were obtained from The Cancer Genome Atlas(TCGA),and differentially expressed genes(DEGs)between TCGA tumor tissue and normal tissue were identified using R programming language.The functions of these DEGs were analyzed via KEGG and GO enrichment.2.Univariate and multifactorial Cox regression analyses were used to identify regression coefficients,which were then weighted to create a risk score for validating the prognostic value of the model for HNSCC.The Gene Expression Omnibus(GEO)database was utilized as an external validation cohort.3.The relationship between the prognostic models in HNSCC patients and tumor immune microenvironment characteristics was then explored.4.The hub genes were further screened based on their clinical significance in HNSCC using the prognostic model.5.The expression analysis and immune cell relationship analysis of the hub genes for pan-cancer and HNSCC were conducted using the TCGA cohort.The co-expression genes of hub genes were identified,and the related biological pathways of hub genes were explored.Finally,the immunohistochemistry was used to investigate the expression and clinical significance of the hub genes/proteins in head and neck cancer tissues.Results:1.The analysis was performed on the ten differentially expressed genes(DEGs)including AIM2,CASP5,GSDMB,GSDMD,GSDME,IL1 B,NLRP1,NLRP6,NLRP7,and ELANE.Three genes(GSDME,NLRP1,and NLRP6)were finally identified for model construction.2.Patients were assigned risk scores based on the model,classifying them into high-risk and low-risk groups.It was observed that patients in the high-risk group had shorter survival times.The ROC curve for overall survival(OS)rate validated that the function of risk prediction was significantly better than that of clinical characteristics such as age,gender,and grade.3.The efficacy of the three-gene signature was also confirmed via the GEO database.The high-risk group,characterized by higher stromal cell scores and immune scores,showed enrichment with T-cell,macrophage,and mast cell infiltration.4.NLRP1 had the most significant prognostic relevance in HNSCC and was closely associated with the N-stage and lymph node transition,making it a hub gene related to scorching death in HNSCC.NLRP1 was found to be significantly differentially expressed between cancer and normal tissues at 15 sites,with high expression in HNSCC tumor tissue.Thirteen co-expressed genes of NLRP1 were identified and GO enrichment analysis revealed biological processes including positive regulation of metabolic and biosynthetic processes,and RNA polymerase transcription.NLRP1 expression was significantly and positively correlated with lymphocyte infiltration in HNSCC,suggesting an enhanced local lymphocytic infiltration of the tumor.Immunohistochemistry revealed significantly higher NLRP1 expression in HNSCC compared to normal tissues,with its high expression associated with higher clinical stage and lymph node metastasis.Conclusions:In this study,a prognostic model was constructed consisting of cell scorch death-related genes(GSDME,NLRP1,and NLRP6),which was found to have prognostic value for HNSCC,with NLRP1 potentially being the hub gene.The development of prognostic models is not only beneficial for exploring new molecular markers for HNSCC,but also for identifying potential targets for its treatment.