Proteomic characterization of airway obstruction-associated proteins in non-smoking lung adenocarcinoma

Lung adenocarcinoma (LUAD) and chronic airway obstruction frequently coexist and are associated with poorer clinical outcomes. Although airway obstruction is recognized as a risk factor for adverse prognosis in LUAD, the molecular alterations associated with airway obstruction in LUAD remain incompletely understood. Most previous studies have been confounded by smoking-related molecular changes.

To identify proteins associated with airway obstruction status in non-smoking patients with LUAD using a proteomics-based approach.

Proteomic analysis was performed on paired tumor and adjacent normal tissues obtained from 12 non-smoking LUAD patients, including 6 patients with airway obstruction and 6 without airway obstruction. A four-group design combined with a three-step intersection strategy was used to identify candidate proteins associated with both airway obstruction status and tumor-related alterations. Functional enrichment, protein-protein interaction (PPI) network analysis, Western blot validation, correlation with pulmonary function, and transcriptomic validation using The Cancer Genome Atlas (TCGA) database were subsequently performed.

A total of 2036 differentially expressed proteins were identified in tumor tissues between airway obstruction and non-obstruction groups. The three-step intersection strategy identified 15 candidate proteins. PPI network analysis and expression-direction consistency screening further identified four core proteins: Cystatin B (CSTB), Bone Morphogenetic Protein Receptor Type 1A (BMPR1A), Complement C4B (C4B), and Potassium Channel Tetramerization Domain Containing 10 (KCTD10). Western blot validation supported the differential expression patterns of these four core proteins in tumor tissues. Functional enrichment analysis indicated involvement in DNA damage repair, immune regulation, and cellular proliferation pathways. CSTB expression was positively correlated with FEV1%, whereas BMPR1A expression showed a negative correlation. TCGA analyses demonstrated that expression of these proteins' corresponding genes was associated with LUAD prognosis, and C4B expression was significantly associated with tumor stage.

This study identified CSTB, BMPR1A, C4B, and KCTD10 as proteins associated with airway obstruction status in non-smoking LUAD patients. These findings provide preliminary insights into molecular differences related to airway obstruction in LUAD and generate candidate biomarkers for future validation studies. Western blot validation provided additional experimental support for the proteomic findings. Larger multicenter cohorts and functional experiments are required to clarify the biological and clinical significance of these proteins.