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

肺癌合并肺纤维化患者血清生物标志物的变化及其与患者生存预后的相关性

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Abstract

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 [PO(2)], 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.

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