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. Diagram of COPD research process involving Th17, biomarkers and candidate agents.The diagram illustrates a research process related to COPD. At the center is COPD, with arrows connecting to various components. The top left shows ’Th17’ with ’immune dysregulation.’ The bottom left features ’Transcriptomics’ and ’Machine learning.’ The bottom center displays ’Biomarkers’ with ’TGFBR2’ and ’IKBKB’ both showing downward arrows, linked to ’RT-qPCR.’ The bottom right depicts ’Th17-related alteration’ with connections to ’JAK-STAT,’ ’TLR,’ and ’NOD.’ The top right shows ’Candidate agents’ with ’future validation.’ Arrows indicate the flow between these components, suggesting a cycle of research and validation.