Abstract
Background: Noncystic fibrosis (non-CF) bronchiectasis is a chronic respiratory disease characterized by irreversible bronchial dilation, with an increasing global prevalence and substantial clinical burden. Despite the advances in symptomatic management, the underlying molecular mechanisms remain poorly understood. Transcription factor DP-1 (TFDP1) and cell division cycle protein 27 (CDC27), which are implicated in tumorigenesis and cell cycle regulation, have not been explored in bronchiectasis. Methods: Gene expression data from the Gene Expression Omnibus dataset GSE97298 (27 patients with bronchiectasis vs. nine healthy controls) were analyzed to identify differentially expressed genes (DEGs) using edgeR (log2 fold-change value ≥ 1.2, adj.p < 0.05). Protein-protein interaction (PPI) networks were constructed using STRING software. Clinical validation included 71 patients with bronchiectasis and 29 healthy controls. TFDP1 and CDC27 mRNA levels were quantified using real-time polymerase chain reaction. Regulatory relationships were assessed using ChIP-seq data (Cistrome DB), and pathway enrichment was performed using clusterProfiler to explore the potential molecular mechanisms of action of TFDP1 and CDC27 in non-CF bronchiectasis. Results: In total, 355 DEGs were identified (45 upregulated and 310 downregulated genes). TFDP1 and CDC27 were significantly upregulated in patients with bronchiectasis (p < 0.01) and exhibited a strong positive correlation (r = 0.6104, p < 0.0001). ChIP-seq confirmed TFDP1 binding to the CDC27 promoter region. Enrichment analysis revealed TFDP1-associated DEGs involved in the cell cycle. TFDP1 expression was correlated with the bronchiectasis severity index (r = 0.2904, p < 0.05). Conclusion: This study demonstrated the synergistic upregulation of TFDP1 and CDC27 in bronchiectasis and explored cell cycle regulation as an important potential mechanism by which TFDP1 and CDC27 contribute to the development of bronchiectasis. Therefore, TFDP1 may serve as a biomarker of disease severity.