Identification of pyroptosis‐related gene prognostic signature in head and neck squamous cell carcinoma

AbstractBackgroundHead and neck squamous cell carcinoma (HNSCC) is a life‐threatening disease with poor prognosis. Pyroptosis has been recently disclosed as a programmed cell death triggered by invasive infection, involved in cancer development. However, the prognosis role of pyroptosis‐related genes in HNSCC has not been discussed.MethodsThe RNA sequence data of pyroptosis‐related genes were obtained from The Cancer Genome Atlas (TCGA) database. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were performed to screen the HNSCC survival‐related signature genes. We established a HNSCC risk model with the identified prognostic genes, then divided the HNSCC patients into low‐ and high‐risk subgroups according to median risk score. Moreover, we utilized Gene Expression Omnibus (GEO) dataset to validate the risk model. Go and KEGG analyses were conducted to reveal the potential function of differential expression of genes that identified between low‐ and high‐risk subgroups. ESTIMATE algorithm was performed to investigate the immune infiltration of tumors. Correlation between signature gene expression and drug‐sensitivity was disclosed by Spearman's analysis.ResultsWe constructed a HNSCC risk model with identified seven pyroptosis‐related genes (CASP1, GSDME, IL6, NLRP1, NLRP2, NLRP6, and NOD2) as prognostic signature genes. High‐risk subgroup of HNSCC patients in TCGA cohort correlated with lower survival probability than patients from low‐risk subgroup (p < .001), and the result is verified with GEO dataset. In addition, 161 genes were identified differentially expressed between the low‐ and high‐risk subgroups in the TCGA cohort, mainly related to immune response. Higher PD‐L1 expression level was found in the high‐risk subgroup that indicated the possible employment of immune checkpoint inhibitors. IL6 was positively correlated with WZ3105 and MPS‐1‐IN‐1 in the cancer therapeutics response portal database.ConclusionWe built and verified a risk model for HNSCC prognosis using seven pyroptosis‐related signature genes, which could predict the overall survival of HNSCC patients and facilitate treatment.