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pmid:40524719

Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD.

Jiale Zhao · Xiahui Ge · Hailong Li · Genfei Jing · Weirong Ma · Yuchun Fan · Juan Chen · Zhijun Zhao · Jia Hou

International journal of chronic obstructive pulmonary disease · 2025 doi:10.2147/COPD.S511696

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Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD.
doi
10.2147/COPD.S511696
pmid
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Jiale Zhao
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Xiahui Ge
[2]
Hailong Li
[3]
Genfei Jing
[4]
Weirong Ma
[5]
Yuchun Fan
[6]
Juan Chen
[7]
Zhijun Zhao
[8]
Jia Hou
journal
International journal of chronic obstructive pulmonary disease
year
2025
abstract
Background: Chronic Obstructive Pulmonary Disease (COPD), a complex respiratory disorder, results from genetic and environmental factors. Uncovering its genetic basis is vital for diagnostics and treatment. Robust genetic analysis is essential to establish a causal link. Methods: Genome-wide DNA methylation analysis was performed using the Illumina Infinium HumanMethylation850 BeadChip in peripheral blood from 8 COPD patients and 8 healthy smoking controls. Differentially methylated genes (DMGs) were cross-analyzed with differentially expressed genes (DEGs) identified from the Gene Expression Omnibus (GEO) dataset GSE38974 (23 COPD, 9 controls). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks were utilized to identify COPD-associated hub genes. Mendelian randomization (MR) analysis examined the causal relationship between hub genes and COPD. The expression of selected hub genes was validated through RT-qPCR (80 COPD, 62 controls), immunohistochemistry, and Western blot analyses (10 COPD and 10 controls). Results: We found 10,593 DMGs and 646 DEGs associated with COPD. These genes were compared with WGCNA module genes, and the Protein-Protein Interaction (PPI) network interaction diagram was drawn, thereby identifying five Hub genes: PPIB, HSPA2, PRPF19, FKBP10 and DOHH. The expression levels of DOHH, FKBP10, PPIB and PRPF19 are higher in COPD, while the expression level of HSPA2 is lower. MR results indicate a potential causal relationship between PRPF19, PPIB and COPD. RT-qPCR, immunohistochemistry and Western blot experiments verified that the expression of PRPF-19 and PPIB was up-regulated in peripheral blood and lung tissue, which was consistent with the results of bioinformatics analysis. Conclusion: Our findings suggest that PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD. Further studies are required to fully elucidate their roles in COPD pathogenesis.
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Uncovering its genetic basis is vital for diagnostics and treatment. Robust genetic analysis is essential to establish a causal link.\nMethods: Genome-wide DNA methylation analysis was performed using the Illumina Infinium HumanMethylation850 BeadChip in peripheral blood from 8 COPD patients and 8 healthy smoking controls. Differentially methylated genes (DMGs) were cross-analyzed with differentially expressed genes (DEGs) identified from the Gene Expression Omnibus (GEO) dataset GSE38974 (23 COPD, 9 controls). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks were utilized to identify COPD-associated hub genes. Mendelian randomization (MR) analysis examined the causal relationship between hub genes and COPD. 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