Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A...

Area of Science:

• Pulmonary Medicine
• Genomics
• Bioinformatics

Background:

• Previous studies identified transcriptomic biomarkers in lung, sputum, and blood for COPD severity.
• The congruence of lung pathobiology with surrogate tissues (sputum, blood) remains unclear.

Purpose of the Study:

• To investigate whether lung pathobiology in COPD is accurately reflected in sputum and blood transcriptomics.
• To identify shared and distinct molecular mechanisms across different tissue types in COPD.

Main Methods:

• Weighted Gene Co-expression Network Analysis (WGCNA) applied to four COPD gene-expression datasets: lung tissues (L1, L2), induced sputum (S), and peripheral blood (B).
• Module preservation analysis to compare transcriptomic similarities across tissues.
• Ontology enrichment analysis to identify biological functions within preserved modules.

Main Results:

• Robust gene co-expression module preservation was observed between two lung tissue datasets (86%).
• Module preservation was significantly lower in sputum (33%) and blood (23%).
• Three modules preserved across lung and sputum (but not blood) were associated with airflow limitation severity (FEV1), enriched for mitochondrial function, ion homeostasis, T cells, and RNA processing genes.

Conclusions:

• Lung tissue transcriptomics in COPD patients are poorly mirrored in sputum and unrelated to blood, indicating independent systemic regulation.
• The findings suggest that sputum and blood are not ideal surrogates for studying lung-specific pathobiology in COPD.
• A module associated with airflow limitation, enriched in mitochondria-related genes, supports the role of mitochondrial dysfunction in COPD pathogenesis.