Serum biomarker changes in pulmonary fibrosis with lung cancer and their correlation with patient survival prognosis

This study aimed to characterize serum tumor markers - cytokeratin 19 fragment (Cyfra21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC) - together with arterial blood gas and pulmonary function parameters (partial pressure of oxygen [PO₂], forced vital capacity [FVC], diffusing capacity of the lung for carbon monoxide [DLCO], DLCO adjusted for alveolar volume [DLCO/VA], and lung reserve rate) in patients with pulmonary fibrosis (PF), lung cancer (LC), and PF combined with lung cancer (PF+LC), and to evaluate their prognostic value for 2-year overall survival (OS) and lung cancer-specific mortality. A retrospective analysis was conducted on 485 PF patients, 135 LC patients, 187 PF+LC patients, and 100 healthy controls enrolled between February 2010 and April 2023. Baseline demographics, tumor markers, and pulmonary function data were compared across groups. Serum markers followed the trend: PF+LC ≈ LC > PF > controls, while pulmonary function was markedly impaired in PF+LC patients compared with PF patients. In PF patients, Cyfra21-1, FVC, DLCO, and age ≥65 years were independent predictors of 2-year OS. For PF+LC patients, Cyfra21-1, FVC, DLCO, age ≥65 years, and fibrosis type were significant prognostic factors, while TNM staging did not correlate with OS. Competing risk analysis identified Cyfra21-1, FVC, fibrosis type, and pirfenidone therapy as independent predictors of lung cancer-specific mortality. These findings demonstrate that serum tumor markers and pulmonary function parameters reflect disease heterogeneity between PF and PF+LC, with Cyfra21-1, FVC, DLCO, age, and fibrosis type serving as important survival determinants. Additionally, pirfenidone therapy may reduce lung cancer-related mortality, underscoring its potential therapeutic benefit in managing PF+LC.