Respiratory
Differential Expression Analysis to Identify Molecular Signatures of Asthma and Chronic Obstructive Pulmonary Disease (COPD) and Asthma-COPD Overlap (ACO) among Smokers Tianjiao Shen* Tianjiao Shen Mohammed S. Orloff
Background:
COPD and asthma often coexist as Asthma-COPD Overlap (ACO), a debated condition lacking clear classification. Patients with ACO experience more severe symptoms, frequent exacerbations, and reduced life quality than those with asthma or COPD alone. Diagnosis of ACO is challenging due to lack of biomarkers to differentiate ACO from asthma or COPD. Hence the need to have distinct identification and well-defined recommendations for ACO.
Methods:
We analyzed 536 whole-blood RNA sequencing data from the COPDGene Study (GSE97531). Participants were classified into asthma, COPD, ACO, and control groups based on FEV1/FVC and post-bronchodilator tests. Quality control and alignment were performed with FastQC and “Spliced Transcripts Alignment to a Reference (STAR) “. Differential expression analysis was conducted using edgeR and limma, identifying significant expressed genes (FDR < 0.05).
Results:
We identified 9 DEGs comparing in ACO vs. asthma, 28 in ACO vs. COPD, 871 in ACO vs. controls, 10 in asthma vs. controls, and 1490 in COPD vs. controls in DE analysis. Notable DEGs distinguishing ACO from asthma/COPD included PAICSP6 (ACO vs. asthma, LogFC = -2.35, FDR = 0.027) and GRHL3-AS1(ACO vs. COPD, LogFC = 1.08, FDR = 0.047). A total of 442 were unique to ACO vs. controls with no significant changes in asthma- or COPD-only comparisons, suggesting their potential as ACO-specific biomarkers. ADGRG7 was significantly differential expressed across multiple asthma-related comparisons (ACO vs. COPD, ACO vs. controls, and Asthma vs. controls), indicating a potential role in asthma-like features within ACO. Additionally, IFI27 was a DEG associated with ACO, asthma, and COPD, suggesting involvement in common lung function mechanisms.
Conclusion:
Transcriptomic and molecular changes identified provide insight into ACO, distinguishing it from asthma and COPD and identifying potential biomarkers for improved disease characterization.