Pyroptosis-related gene signatures are associated with prognosis and tumor microenvironment infiltration in head and neck cancer.

Background And Aims: Recent studies have highlighted the biological significance of pyroptosis in cancer development. Nevertheless, it is still uncertain if pyroptosis also plays a part in immune modulation and the creation of the tumor microenvironment (TME).

Methods: The pyroptosis regulatory genes (PRGs) were comprehensively assessed in 1938 head and neck cancer samples, and systematically correlated these modification patterns with the infiltration characteristics of TME cells. The unsupervised consensus analysis method was used to identify specific pyroptosis clusters. The single-sample gene set enrichment analysis and CIBERSOFT algorithms were used to evaluate the infiltration levels of various immune cell subsets. A principal component analysis algorithm was used to construct the pyrolysis potential index (PPI) to quantify the pyrolysis regulation patterns in head and neck squamous cell carcinoma (HNSC).

Results: Pyrophosphate regulatory genes (PRGs) are often upregulated in tumors due to mutations. PRGs relate to various clinical outcomes and pathways. Molecular subtyping identified pyroptosis patterns, which align with three tumor immunophenotypes: immune-inflamed, immune-excluded, and immune-desert. The PPI measures pyrolysis roles, showing higher PPI in tumor samples linked to subtypes and clinical characteristics. Lower PPI correlates with longer survival, increased immune activity, more tumor mutations, high PD-L1 expression, and mutations in significant genes like PIK3CA. Such patients also experience enhanced immune responses in immunotherapy trials.

Conclusion: We conducted a comprehensive examination of pyroptosis in HNSC and developed a PPI indicator that shows a strong correlation with the variety and intricacy of the TME.