Identification of Th17 Cell-Associated Biomarkers and Their Potential Regulatory Mechanisms in Chronic Obstructive Pulmonary Disease Through Integrated Bioinformatics Analysis and Machine Learning.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and chronic airway inflammation. Th17 cell-related immune pathways may contribute to COPD-associated immune dysregulation, but their molecular associations remain incompletely understood. This study aimed to preliminarily explore Th17 cell-associated biomarkers and their potential regulatory networks in COPD.

METHODS

Transcriptomic profiles from COPD and control samples were analyzed to identify differentially expressed genes (DEGs). Th17 cell-related DEGs were obtained by intersecting DEGs with Th17-related genes. Random forest and Boruta algorithms were used for biomarker screening, followed by expression validation in training and validation cohorts and RT-qPCR verification. A nomogram model was constructed, and chromosome localization, immune infiltration, gene set enrichment analysis (GSEA), regulatory network analysis, and drug prediction were performed.

RESULTS

A total of 3811 DEGs were identified, including 1408 upregulated and 2403 downregulated genes; 16 overlapped with Th17-related genes. AUC was 1.000, with a 95% confidence interval of 1.000-1.000. Machine learning and validation analyses indicated that TGFBR2 and IKBKB may serve as COPD-associated biomarkers, with both genes showing significant downregulation in COPD samples and RT-qPCR validation (p < 0.05). Immune infiltration analysis indicated significant differences in 11 immune cell types between COPD and control groups. TGFBR2 and IKBKB were negatively correlated with Th17 cell infiltration (TGFBR2: cor = -0.502, p < 0.05; IKBKB: cor = -0.466, p < 0.05). IKBKB was also negatively correlated with macrophages (cor = -0.725, p < 0.001), while TGFBR2 was negatively correlated with natural killer T cells (cor = -0.635, p < 0.001). GSEA suggested 78 enriched pathways, including 42 related to TGFBR2 and 36 related to IKBKB. Drug prediction suggested 92 potential agents.

CONCLUSION

This preliminary, hypothesis-generating study suggests that TGFBR2 and IKBKB may be associated with Th17-related immune alterations in COPD and may provide candidate markers for further mechanistic and therapeutic validation.