Wenhui Fu, Yangli Liu, Renjie Li, Haiying Jin

Department of Respiratory Medicine, Jinyun People’s Hospital, Lishui, Zhejiang, 321400, People’s Republic of China

Correspondence: Haiying Jin, Department of Respiratory Medicine, Jinyun People’s Hospital, No. 299 North Ziwei Road, Wuyun Street, Lishui, Zhejiang, 321400, People’s Republic of China, Tel +86 13754278979, Email jinhaiying8979@yeah.net

Background: Chronic obstructive pulmonary disease (COPD) involves progressive lung function decline, with hypoxia playing a key pathogenic role. However, systematic investigations focusing on hypoxia-related genes (HRGs) in COPD remain limited.
Methods: We applied machine learning to identify HRG-associated diagnostic biomarkers and evaluated their performance via Receiver Operating Characteristic (ROC) analysis. Mendelian randomization (MR) was conducted to assess causal relationships between candidate genes and COPD. A nomogram model was constructed to evaluate clinical utility, and a ceRNA network was developed using ENCORI database.
Results: Six HRG-based diagnostic biomarkers were identified, including SLC2A1, which demonstrated strong diagnostic value (AUC > 0.8). MR analysis revealed a significant causal effect of SLC2A1 expression on COPD risk (OR = 1.32, 95% CI: 1.02– 1.71, P < 0.05). Functional evidence suggests SLC2A1 promotes hypoxia-induced metabolic reprogramming in airway epithelial cells. The constructed nomogram showed good clinical applicability. ceRNA analysis highlighted MALAT1, NEAT1, and XIST as potential upstream regulators.
Conclusion: Our findings identify SLC2A1 as a causal and diagnostically relevant gene in COPD, offering novel insight into hypoxia-driven disease mechanisms and supporting future personalized therapeutic strategies.

Keywords: chronic obstructive pulmonary disease, hypoxia-related genes, Mendelian randomization, machine learning