The NLRP1 inflammasome emerges as a promising therapeutic target and prognostic biomarker across multiple cancer types: A comprehensive pan-cancer analysis

Abstract

Aims: Nod-like receptor family pyrin domain containing 1 (NLRP1) serves as the central component of the inflammasome complex and has emerged as a potential contributor to cancer development. Despite accumulating evidence, a comprehensive assessment of NLRP1 across various cancer types has yet to be undertaken. Main Methods: Several databases have evaluated NLRP1 expression across various cancer types in The Cancer Genome Atlas (TCGA). Additionally, studies have investigated the correlation between NLRP1 and various survival metrics, infiltration of cancer-associated fibroblasts, genetic alterations, drug sensitivity, and promoter methylation. Furthermore, research has explored the potential roles of NLRP1 and its interactions with other proteins. Key Findings: Our analysis revealed decreased expression of NLRP1 in BLCA, BRCA, KICH, LUAD, LUSC, PRAD, and UCEC tumor tissues compared to normal tissues. We identified a significant correlation between NLRP1 expression and various cancer survival parameters, genetic mutations, and immune infiltration of cancer-associated fibroblasts. Furthermore, we observed that NLRP1 expression is regulated by promoter DNA methylation in ESCA. Abnormal expression of NLRP1 was associated with decreased sensitivity to multiple anti-tumor drugs and small compounds. NLRP1 was found to be involved in pathways associated with T cell receptors and chemokines. Significance: Reduced NLRP1 expression contributes to cancer progression and holds potential as a crucial biomolecular marker for diagnostic, prognostic, and personalized therapeutic interventions across different malignancies.