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This study aims to identify key genes linked to both CRSwNP and SGs, offering novel perspectives for improving CRSwNP treatment and management. Data from GSE136825, GSE179265, and SG-related gene sets were retrieved from public databases. Key genes were identified via machine learning, ROC analysis, and expression validation. Subsequently, nomogram construction, Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and drug prediction were performed to explore the regulatory mechanisms of these genes. Three candidate genes\u2014ANG, CRYAB, and FBP1\u2014passed ROC and expression validation and were ultimately identified as key players. GSEA revealed that these genes collectively participate in the cell cycle pathway. Immune infiltration analysis showed 23 differentially abundant immune cell types between the CRSwNP and control groups, with ANG, CRYAB, and FBP1 all exhibiting significant positive correlations with Type 2 T helper cells. 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