Identification and validation of biomarkers related to lysine β-hydroxybutyrylation in chronic obstructive pulmonary disease based on transcriptomics data.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: This study identified POLD2 and OTUD7B as biomarkers for COPD, offering valuable insights that could support the development of targeted therapies.