Computational biology and chemistry · 2025
Identification of DNA damage repair-related diagnostic markers for idiopathic pulmonary fibrosis via WGCNA.
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Rao Xiao, Zhou Yiling, Xue Jianbo, Zhou Zhiyou
Аннотация
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown etiology with limited diagnostic and therapeutic options. DNA damage repair (DDR) plays an important role in the pathogenesis of lung diseases. The aim of this study was to identify core DDR genes involved in IFP progression and to assess their diagnostic potential and immunological relevance.
METHODS: Utilizing Gene Expression Omnibus (GEO) database and previous research, we obtained publicly available IPF disease data and DDR gene set data. Through WGCNA, LASSO, and protein-protein interaction (PPI) network analysis, we identified DDR-related hub genes, which were subsequently validated using external validation sets. ROC analysis was employed to assess and identify IPF diagnostic markers. Immune microenvironment of IPF group and its correlation with diagnostic genes were evaluated by ssGSEA algorithm and Spearman correlation analysis. Potential miRNAs and functional genes regulating diagnostic genes were predicted utilizing Network Analyst and GeneMANIA platforms.
RESULTS: We identified HMGB2 and PRPF19 as diagnostic markers for IPF, both of which exhibited excellent diagnostic performance across three datasets. Comparisons at both single-cell and transcriptome levels revealed that HMGB2 was overexpressed in IPF, while PRPF19 was underexpressed. Immune microenvironment assessments indicated high infiltration of macrophages and neutrophils in IPF group, suggesting presence of an inflammatory fibrotic immune microenvironment. Correlation analysis showed that various immune cells in IPF immune microenvironment were significantly associated with HMGB2 and PRPF19, indicating that these genes may influence immune microenvironment.
CONCLUSION: By combining WGCNA and LASSO analyses, this study identified two hub genes, HMGB2 and PRPF19, that can serve as diagnostic markers for IPF and modulate its immune microenvironment. This finding provides new directions for clinical diagnosis of IPF and research into DDR-related mechanisms.
METHODS: Utilizing Gene Expression Omnibus (GEO) database and previous research, we obtained publicly available IPF disease data and DDR gene set data. Through WGCNA, LASSO, and protein-protein interaction (PPI) network analysis, we identified DDR-related hub genes, which were subsequently validated using external validation sets. ROC analysis was employed to assess and identify IPF diagnostic markers. Immune microenvironment of IPF group and its correlation with diagnostic genes were evaluated by ssGSEA algorithm and Spearman correlation analysis. Potential miRNAs and functional genes regulating diagnostic genes were predicted utilizing Network Analyst and GeneMANIA platforms.
RESULTS: We identified HMGB2 and PRPF19 as diagnostic markers for IPF, both of which exhibited excellent diagnostic performance across three datasets. Comparisons at both single-cell and transcriptome levels revealed that HMGB2 was overexpressed in IPF, while PRPF19 was underexpressed. Immune microenvironment assessments indicated high infiltration of macrophages and neutrophils in IPF group, suggesting presence of an inflammatory fibrotic immune microenvironment. Correlation analysis showed that various immune cells in IPF immune microenvironment were significantly associated with HMGB2 and PRPF19, indicating that these genes may influence immune microenvironment.
CONCLUSION: By combining WGCNA and LASSO analyses, this study identified two hub genes, HMGB2 and PRPF19, that can serve as diagnostic markers for IPF and modulate its immune microenvironment. This finding provides new directions for clinical diagnosis of IPF and research into DDR-related mechanisms.