Pyroptosis, as a novel identified programmed cell death, is closely correlated with tumor immunity and shows potential roles in cancer treatment. Discerning a pyroptosis-related gene signature and its correlations with tumor immune microenvironment is critical in head and neck squamous cell carcinoma (HNSCC). Transcriptome data and corresponding clinical data were downloaded from TCGA and GEO databases. Tumor mutation burden (TMB) data were obtained from TCGA database. Firstly, univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct a six pyroptosis-related gene signature. Kaplan–Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA) results verified that the risk model has good performance in predicting the survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the pyroptosis-related gene signature was immune related. Finally, the immune landscape and immunotherapy sensitivity prediction capabilities of the risk model were further explored. There were close correlations between the overall survival (OS) and various immune cells and immune functions. Single-sample gene set enrichment analysis (ssGSEA) showed that high risk group had decreased expression of various immune cells and lower activities of immune functions. Meanwhile, tumor mutation burden (TMB) data combining risk score could well predict the OS of HNSCC patients. However, tumor immune dysfunction and exclusion (TIDE) analysis revealed that there was no significant difference in the sensitivity to immunotherapies between high and low risk groups. Finally, a nomogram based on risk score and clinicopathological parameters was constructed. And, the risk model demonstrated better sensitivity and specificity than TIDE scores and T-cell-inflamed signature (TIS). In conclusion, although the risk model could not well predict the immune escape and response to immunotherapies, the signature established by pyroptosis-related genes, with better sensitivity and specificity than TIDE scores and TIS signature, could be used for predicting prognosis and immune status of HNSCC patients.

BackgroundCalcium-dependent protein copine 8 (CPNE8), a new member of Copine family, emerges important roles in malignancies. However, the expression and potential role of CPNE8 in pan cancer remain unclear. Methods: Pan cancer analysis of CPNE8 expression in 33 types of cancers were based on data downloaded from the University of California Santa Cruz (UCSC) Xena database. The clinical significances of CPNE8 were analyzed using Cox regression analysis and Kaplan Meier survival analysis. Correlations between CPNE8 expression and tumor immune microenvironment were assessed using ESTIMATE algorithm, CIBERSORT analysis and online database TISIDB. The correlations between CPNE8 expression and tumor mutation burden (TMB), microsatellite instability (MSI) status and response to immune checkpoint inhibitors (ICIs) were further explored. Moreover, competitive endogenous RNA (ceRNA) networks related to CPNE8 and its correlations with immune cell related genes were further studied in stomach adenocarcinoma (STAD).Results: Differential expression of CPNE8 were identified in 14 types of cancers. Differential expression of CPNE8 could predict tumor stage or prognosis of various cancer patients. Pan cancer analysis indicated that CPNE8 demonstrated oncogenic role in STAD, head and Neck squamous cell carcinoma (HNSC) and esophageal carcinoma (ESCA), and tumor suppressive role in thyroid carcinoma (THCA). These four cohorts were selected for further study due to their consistent results in expression and prognostic values. Gene set enrichment analysis (GSEA) revealed that CPNE8 might regulate several key immune-related signaling pathways. Furthermore, CPNE8 expression was significantly correlated with the infiltration of different subtypes of immune cells, TMB and MSI. Moreover, PWAR5 and LIFR-AS1 could sponge miR-222-3p as ceRNAs to regulate the expression of CPNE8 in STAD. In addition, CPNE8 was significantly correlated with the expression of immune cell related genes, such as CD8 T cells, macrophages, B cells and dendritic cells in STAD.Conclusion: This study demonstrated that CPNE8 could serve as a promising biomarker associated with the prognosis and immune microenvironment in several malignancies.