Prognostic Significance of Pyroptosis-Related Genes in Pulmonary Fibrosis: A Risk Scoring Model Approach

<bold>Background:</bold> Pulmonary fibrosis is a deadly lung disease with unclear mechanisms. This study explores the prognostic potential of pyroptosis-related genes in the condition. <bold>Objective:</bold> We aim to elucidate the pathogenesis of pulmonary fibrosis and identify prognostic biomarkers through the expression of pyroptosis-related genes. <bold>Methods:</bold> We assessed 30 pyroptosis-related genes in the GSE70866 dataset, discerning 11 differentially expressed ones. Subsequent analyses included correlation matrices, PPI, TFI, and miRNA networks. In GSE110147, 23 genes were found different, with 7 overlapping with GSE70866. NMF categorized molecular subtypes; survival associations and prognostic genes were identified via univariate Cox and LASSO regressions. Immune infiltration was linked to patient survival through multifactorial Cox regression, validated externally. <bold>Results:</bold> GSE70866 showed 11 differentially expressed pyroptosis genes. Sex and GAP index influenced these variations. GSE110147's 23 genes included 7 from GSE70866, with network analyses revealing critical interactions. Four molecular subtypes exhibited distinct survival outcomes. Five genes (CASP1, IL1B, IL6, NLRC4, NLRP3) were prognostic. Their risk score predicted survival well, with immune cell correlations confirming the findings. The risk stratification was effective, with GSE28221 validating NLRP3's prognostic significance. <bold>Conclusions:</bold> The study highlights pyroptosis-related genes as differential expression markers in pulmonary fibrosis and presents a new risk score for prognosis, enhancing patient management through the combined use of GAP and risk scores