Chronic obstructive pulmonary disease (COPD) involves progressive lung inflammation and tissue destruction. Lysine β-hydroxybutyrylation (Kbhb) is linked to COPD. This study aimed to identify Kbhb-related biomarkers for COPD to aid therapeutic development. COPD data and Kbhb-related genes (Kbhb-RGs) were obtained from public databases and literature. Candidate genes were identified by overlapping differentially expressed genes (DEGs) with Kbhb-RGs. Biomarkers were selected using machine learning. Diagnostic efficacy was evaluated via a nomogram. Functional enrichment, immune infiltration, drug prediction, and molecular docking analyses were performed. Biomarker expression was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). A total of 12 candidate genes were detected at the intersection of 765 DEGs and 1,493 Kbhb-RGs. Subsequently, POLD2 and OTUD7B were identified as biomarkers, and the expression of these 2 genes was found to be downregulated in COPD samples. The nomogram developed utilizing these biomarkers demonstrated a satisfactory capacity for differentiating among various sample types. Biomarkers were significantly enriched in transcriptional regulation and translation processes. Regulatory T cells displayed a significant positive linkage with OTUD7B (correlation (r) > 0.3, P < 0.05). Eosinophils were considerably negatively relevant to POLD2 and OTUD7B (r < -0.3, P < 0.05). Molecular docking studies demonstrated a strong binding affinity between biomarkers and estradiol. Compared with the control group, the expression levels of POLD2 and OTUD7B were significantly lower in the COPD group. This study identified POLD2 and OTUD7B as biomarkers for COPD, offering valuable insights that could support the development of targeted therapies.
Lei et al. (2026) studied this question.