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

Area of Science:

• Genomics
• Respiratory Medicine
• Molecular Biology

Background:

• Chronic Obstructive Pulmonary Disease (COPD) is a complex respiratory disorder influenced by genetic and environmental factors.
• Understanding the genetic underpinnings of COPD is crucial for developing effective diagnostics and treatments.
• Identifying causal genetic links is essential for advancing COPD research.

Purpose of the Study:

• To identify genetic factors contributing to Chronic Obstructive Pulmonary Disease (COPD).
• To explore the causal relationship between specific genes and COPD.
• To validate potential diagnostic biomarkers for COPD.

Main Methods:

• Genome-wide DNA methylation analysis and gene expression profiling (GEO dataset GSE38974).
• Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis to identify hub genes.
• Mendelian randomization (MR) analysis for causal inference and RT-qPCR, immunohistochemistry, and Western blot for validation.

Main Results:

• Identified 10,593 differentially methylated genes (DMGs) and 646 differentially expressed genes (DEGs) in COPD.
• Five hub genes (PPIB, HSPA2, PRPF19, FKBP10, DOHH) were identified, with PRPF19 and PPIB showing significant associations.
• Validation confirmed upregulation of PRPF19 and PPIB expression in COPD patients' peripheral blood and lung tissue.

Conclusions:

• PRPF19 and PPIB show potential as diagnostic biomarkers for COPD.
• These genes may play a significant role in the pathogenesis of COPD.
• Further research is warranted to fully understand the role of PRPF19 and PPIB in COPD.