A Novel Pyroptosis Prognostic Model Centers on NLRC4 in Colorectal Cancer

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, necessitating the discovery of novel biomarkers and therapeutic targets. This study investigates the role of pyroptosis-related genes (PRGs) in CRC through comprehensive bioinformatics analysis. We identified 202 PRGs from the MSigDB, Gene, and GeneCards databases, of which 159 were differentially expressed in CRC tissues compared to normal tissues. Functional enrichment analysis revealed significant involvement of these genes in pathways such as pyroptosis, cytokine production regulation, and inflammasome complex formation. The KEGG analysis highlighted pathways including NOD-like receptor signaling and necroptosis. A protein-protein interaction (PPI) network identified CASP1, NLRP3, PYCARD, NLRC4, and AIM2 as core genes, with subsequent validation showing decreased expression of CASP1, NLRP3, NLRC4, and AIM2 in CRC tissues. Immune infiltration analysis indicated that NLRP3, CASP1, AIM2, and NLRC4 are associated with immune cell infiltration in CRC. Diagnostic efficacy assessment using ROC curves demonstrated that NLRP3 and NLRC4 have excellent potential as diagnostic biomarkers. Prognostic analysis revealed that high expression of CASP1 correlates with favorable prognosis, while high NLRC4 expression is linked to poor prognosis. A predictive nomogram model incorporating NLRC4 and clinical indicators showed strong predictive capability for overall survival in CRC patients. Immunohistochemical validation confirmed the expression patterns of core genes in CRC tissues. This study underscores the potential of PRGs as biomarkers and therapeutic targets in CRC, offering insights into their role in tumorigenesis and immune modulation. Future research should focus on validating these findings in larger cohorts to enhance the clinical applicability of these biomarkers in CRC management.