Prognosis and Characterization of Immune Microenvironment in Head and Neck Squamous Cell Carcinoma through a Pyroptosis-Related Signature

Abstract

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.

Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma

“…After establishing a positive correlation between the expression of each pyroptosis-related gene and the PRGscore, we found that higher PRGscore were associated with worse prognosis of HNSCC. Our study, similar to these previous studies ( Lu et al, 2022 ; Shen et al, 2021 ; Zhu et al, 2021 ; Li et al, 2022 ; Liu et al, 2019 ), focuses on identifying new biomarkers and predictive models to improve the prognosis and treatment response of cancer patients through machine learning. Prior studies have generally utilized the least absolute shrinkage and selection operator (LASSO) to construct pyroptosis-related molecular features for predicting the survival and prognosis of HNSCC patients ( Lu et al, 2022 ; Shen et al, 2021 ; Zhu et al, 2021 ; Li et al, 2022 ), which is markedly differed from our study design in two key aspects.…”

“…Our study, similar to these previous studies ( Lu et al, 2022 ; Shen et al, 2021 ; Zhu et al, 2021 ; Li et al, 2022 ; Liu et al, 2019 ), focuses on identifying new biomarkers and predictive models to improve the prognosis and treatment response of cancer patients through machine learning. Prior studies have generally utilized the least absolute shrinkage and selection operator (LASSO) to construct pyroptosis-related molecular features for predicting the survival and prognosis of HNSCC patients ( Lu et al, 2022 ; Shen et al, 2021 ; Zhu et al, 2021 ; Li et al, 2022 ), which is markedly differed from our study design in two key aspects. First, as most previous studies have identified several key genes from 33 pyroptosis genes using a LASSO regression model ( Breiman, 1995 ; Tibshirani, 1996 ), our study aims to construct a new prognostic prediction signature based on 4 genes reported to implicate in the pyroptosis of HNSCC.…”

“…Pyroptosis has been implicated in the therapeutic response of tumors to chemotherapy ( Inoue & Tani, 2014 ; Aoto et al, 2018 ; Zhang et al, 2021 ; Gao et al, 2020 ) and immunotherapy ( Zhou et al, 2020 ; Gao et al, 2022 ; Zhang et al, 2022 ). Several previous studies have evaluated the predictive or prognostic value of pyroptosis in HNSCC by employing least absolute shrinkage and selection operator (LASSO) Cox regression analyses based on various pyroptosis-related gene or lncRNA signatures ( Lu et al, 2022 ; Shen et al, 2021 ; Zhu et al, 2021 ; Li et al, 2022 ); however, the studies screened out genes that were more highly correlated with patients’ survival, but ignoring the direct representing potential of these genes for pyroptotic activity. So far, four pyroptosis-related genes are reported to implicate in the progression of HNSCC.…”

A novel stemness-hypoxia-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma

“…The TIDE algorithm could find biomarkers to predict the efficacy of ICBs through a comprehensive analysis of hundreds of different tumor expression profiles, and its prediction effect is significantly better than the existing biomarkers. Although the developers of the TIDE algorithm state that it may not apply to other therapies than melanoma and non-small cell lung cancer (NSCLC), many studies have shown that the application of the TIDE algorithm can be extended to other tumors besides melanoma and NSCLC, such as HCC [ 57 ], breast cancer [ 58 ], head and neck squamous cell carcinoma [ 59 ], and other tumors [ 60 ]. The TIDE algorithm can well help us estimate the immunotherapy response of HCC patients [ 61 , 62 ].…”

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma

“…In OSCC, tumours with high expression of GSDME increased the number of infiltrating CD8 + T cells, granzyme B, and M1 phenotypic macrophages. At the same time, cellular pyroptosis induced by GSDME-mediated chemotherapy played an essential role in the antitumour response [ 206 , 208 ]. The activation of pyroptosis can trigger the efficacy of various antineoplastic drugs.…”