The Inflammasomes Adaptor Protein PYCARD Is a Potential Pyroptosis Biomarker Related to Immune Response and Prognosis in Clear Cell Renal Cell Carcinoma

SIMPLE SUMMARY: Inflammation has been recognized as one of the hallmarks of cancers. PYCARD, the adaptor protein of inflammasomes, plays an important role in pyroptosis and apoptosis. However, the function of PYCARD remains unclear in human cancers. Here, we systematically performed a comprehensive analysis of PYCARD expression and its relationship with immunotherapy response and prognosis. We found significant differences in PYCARD expression between tumor and normal tissue, particularly in clear cell renal cell carcinoma. We also found that PYCARD was an unfavorable prognostic factor and was confirmed by external validation cohorts. Exploration of the profound mechanisms of PYCARD might help to identify new therapeutic targets and improve the efficacy of immunotherapy. ABSTRACT: PYCARD is a protein engaged in inflammation, pyroptosis, and apoptosis. However, the function of PYCARD in human cancers remains unclear. The objective of our study was to explore PYCARD expression and prognostic value in human cancers. Public databases were used to assess PYCARD expression and prognostic value. The TISIDB database was used to explore the associations between PYCARD expression and different immune subtypes. The correlations between PYCARD expression and ICP genes, MMR genes, MSI, and TMB were also investigated. The immunotherapy response was assessed using the TIDE database. Single-cell RNA databases evaluated the PYCARD expression of immune cells. External datasets and immunohistochemical staining were conducted to validate PYCARD expression and prognostic value. The results showed that PYCARD expression varied in several cancers and was associated with prognosis, immune-related genes, published biomarkers, and immunotherapy response. Of note, PYCARD expression was upregulated in renal cancers with high diagnostic ability. Upregulation of PYCARD was correlated with worse prognosis in KIRC and external validation cohorts. In conclusion, PYCARD demonstrated strong correlations with prognosis, immune response, and disease progression in pan-cancer analysis. In ccRCC, PYCARD might serve as a biomarker for diagnosis and therapeutic target-boosting immunotherapy response.