Serum Krebs von den Lungen-6 as a potential biomarker for early diagnosis of silicosis: a case-control study

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Abstract

Background: Silicosis is an irreversible and progressive pulmonary fibrosis that results in prolonged inhalation of crystalline silica. Despite its significant impact, no specific blood biomarkers currently exist for the early diagnosis of this disease. This study aims to evaluate the levels of Krebs von den Lungen-6 (KL-6) in patients with early-stage silicosis and explore its potential as a diagnostic biomarker. Methods: Blood samples were collected from 40 stage I silicosis patients, 57 dust-exposed workers (DEWs), and 70 healthy controls (HCs). The concentrations of KL-6, C-reactive protein (CRP), and angiotensin-converting enzyme (ACE) were measured using the automatic biochemical analyzer. Receiver operating characteristic (ROC) curve analysis was utilized to evaluate the diagnostic efficacy of KL-6, in combination with other biomarkers for the early stage of silicosis. The association between lung function and KL-6 levels in silicosis patients was evaluated using partial correlation analysis. Results: Serum levels of KL-6, CRP, and ACE were remarkably elevated in stage I silicosis patients compared to HCs and DEWs. KL-6 demonstrated an adjusted area under the curve (AUC) of 0.770 for distinguishing stage I silicosis patients from HCs, with a sensitivity of 80.0% and a specificity of 70.0%. When comparing silicosis patients to DEWs, KL-6 alone achieved an adjusted AUC of 0.735, with sensitivity and specificity of 45.0% and 89.5%, correspondingly. The integration of KL-6, CRP, and ACE demonstrated the highest diagnostic efficacy among all tested combinations. Furthermore, serum KL-6 levels were negatively correlated with vital capacity (VC) in silicosis patients. Conclusions: Serum KL-6 may serve as a potential biomarker for early silicosis diagnosis. Its diagnostic performance is significantly improved when combined with CRP ad ACE, offering a potential multi-biomarker approach for enhanced detection in the early stages of the disease. Further validation in larger and more diverse populations is needed to confirm its clinical utility.

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Nong, Q., Zhu, X., Zhong, L., Li, Y., Yao, L., Hu, Z., … Xia, L. (2025). Serum Krebs von den Lungen-6 as a potential biomarker for early diagnosis of silicosis: a case-control study. BMC Pulmonary Medicine, 25(1). https://doi.org/10.1186/s12890-025-03820-9

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