Radiologic phenotype-specific transcriptomic signatures in lung tissues from patients with Mycobacterium avium...

The incidence of Mycobacterium avium complex (MAC)-pulmonary disease (PD) is increasing in South Korea, posing significant diagnostic and therapeutic challenges. Treatment guidelines recommend initiating therapy after serial computed tomography monitoring. Patients with the nodular bronchiectatic (NB) form often respond positively to drug therapy, whereas those with the fibrocavitary (FC) form frequently experience persistent disease despite treatment. Identifying phenotype-specific transcriptomic biomarkers could improve early diagnosis and inform personalized therapeutic strategies.

We utilized surgically resected lung specimens from 21 MAC-PD patients, a valuable clinical resource, as lung surgery is uncommon in MAC-PD management. Each patient provided paired samples of affected and unaffected lung tissues, enabling direct transcriptomic comparisons. Quantitative RNA sequencing was performed on samples from 11 NB and 10 FC cases. Comprehensive bioinformatics and in silico analyses, including gene ontology (GO) and protein-protein interaction (PPI) network analyses, were conducted to identify key diagnostic signatures and biological pathways.

RNA sequencing revealed distinct and shared transcriptomic signatures correlated with radiological phenotypes. GO and PPI analyses identified significant gene clusters involved in B cell proliferation and immune regulation across both NB and FC forms. Additionally, NB-specific signatures highlighted genes predominantly regulating antimicrobial immune responses, while FC-specific signatures enriched genes related to extracellular matrix remodeling.

This study is the first to characterize transcriptomic differences between MAC-PD phenotypes using paired lung tissue samples. Although the identified transcriptomic markers require functional validation, their strong correlation with radiologic subtypes provides preliminary evidence supporting their potential diagnostic value. These findings lay the groundwork for precision diagnostics in MAC-PD and require further validation in larger patient cohorts and through functional assays.