Comparative transcriptomic profiling between two radiologic phenotypes in lungs from patients with pulmonary disease caused by Mycobacterium avium complex

The incidence of Mycobacterium avium complex (MAC)-induced pulmonary disease (PD) has been increasing in South Korea, posing considerable challenges in treatment. Treatment guidelines recommend initiating therapy after serial computed tomography (CT) monitoring. While drug treatment often improves outcomes in patients with the nodular bronchiectatic (NB) form, those with the fibrocavitary (FC) form may continue to experience persistence despite treatment. Our objective was to classify type-specific and common genes based on radiological phenotypes (NB and FC) using RNA sequencing to analyze the cellular landscape of 11 NB sections, 10 FC sections, and 21 unaffected sections from 21 MAC-PD cases. Predictive in silico analysis indicated a significant role for genes related to B cell proliferation and regulation in both forms. Additionally, NB patients exhibited predominantly regulated antimicrobial immune responses, whereas FC patients showed enrichment in genes related to extracellular matrix structure. These target genes identified through genetic analysis could potentially serve as predictive biomarkers for type-specific biological processes and cellular pathways, necessitating further validation studies. To examine biological variances between two distinct clinical phenotypes (NB or FC forms) based on unaffected sections, lung tissue was procured in pairs from each patient. Then, one sample originated from an affected lesion, and the other was extracted from an unaffected region. Resection criteria included consideration of the cavity lesion in FC form or the bronchiectasis lesion in NB form, along with the unaffected area.