Multidimensional biomarker profiling of bronchoalveolar lavage fluid for diagnostic and prognostic evaluation of lung cancer: a retrospective observational study.

[BACKGROUND] Lung cancer remains a leading cause of cancer-related mortality worldwide. This study evaluated multidimensional biomarkers in bronchoalveolar lavage fluid (BALF) for the diagnosis and prognostic evaluation of lung cancer.

[METHODS] This retrospective observational study included 100 patients who underwent clinically indicated bronchoscopy between April 2022 and April 2024, comprising 65 patients with histopathologically confirmed lung cancer and 35 patients with benign pulmonary diseases. BALF data obtained during routine clinical care were retrospectively collected for tumor markers (CEA, CYFRA21-1, NSE, ProGRP), cytokines (IL-6, IL-8, TNF-, IL-10), ctDNA mutation profiles, and immune-cell subpopulations. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Overall survival (OS) was analyzed using Kaplan-Meier methods and Cox proportional hazards regression.

[RESULTS] BALF concentrations of CEA, CYFRA21-1, NSE, ProGRP, IL-6, IL-8, and TNF- were significantly higher in lung cancer patients than in benign controls, whereas IL-10 was lower, resulting in a markedly elevated IL-6/IL-10 ratio (all  < 0.05). ctDNA was detected more frequently in BALF than in peripheral blood (87.7% vs. 64.6%,  = 0.002), with higher variant allele frequencies and greater concordance with tissue genotyping (86.8%). Immune profiling showed increased regulatory T-cell proportions and M2 macrophage polarization with reduced CD8 T-cell proportions in lung cancer BALF. In multivariable Cox analysis, advanced TNM stage, IL-6/IL-10 ratio >15, and CD8/Treg ratio <1.5 were independent predictors of poorer OS.

[CONCLUSION] BALF provides tumor-proximal diagnostic and prognostic information in lung cancer. Enriched tumor markers, inflammatory imbalance, particularly the IL-6/IL-10 ratio, enhanced ctDNA detection, and local immunosuppressive immune features support the utility of BALF as a minimally invasive liquid biopsy for lung cancer evaluation and risk stratification.