| Summary: | Zhifei Hou,1,2 Xinran Zhang,3 Yong Gao,4 Jing Geng,2 Yu Jiang,5 Huaping Dai,1,2 Chen Wang1,2 1Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Clinical Research and Data Management, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Sinopharm Tongmei General Hospital, Datong, Shanxi Province, People’s Republic of China; 5Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Huaping Dai; Chen Wang, Email daihuaping@ccmu.edu.cn; cyh-birm@263.netBackground: Coal worker’s pneumoconiosis (CWP) is a chronic occupational disease mainly caused by coal dust inhalation in miners. This study aimed to investigate the clinical value of Osteopontin (OPN), KL-6, Syndecan-4 and Gremlin-1 as serum biomarkers in CWP.Patients and Methods: We integrated reported lung tissues transcriptome data in pneumoconiosis patients with silica-exposed alveolar macrophage microarray data to identify four CWP-associated serum biomarkers. The serum concentrations of Osteopontin, Krebs von den Lungen-6 (KL-6), Syndecan-4 and Gremlin-1 were measured in 100 healthy controls (HCs), 100 dust-exposed workers (DEWs) and 200 patients of CWP. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity, specificity, cut-off value and area under the curve (AUC) value of biomarkers.Results: The pulmonary function parameters decreased sequentially, and the serum OPN, KL-6, Syndecan-4 and Gremlin-1 concentrations were increased sequentially among the HC, DEW and CWP groups. Among all participants, multivariable analysis revealed that these four biomarkers were negatively correlated with the pulmonary function parameters (all p< 0.05). Compared with HCs, patients with higher OPN, KL-6, Syndecan-4 and Gremlin-1 had higher risk for CWP. The combination of OPN, KL-6, and Syndecan-4 can improve the diagnostic sensitivity and specificity of CWP patients differentiated from HCs or DEWs.Conclusion: OPN, KL-6 and Syndecan-4 are novel biomarkers that can be used for CWP auxiliary diagnosis. The combination of three biomarkers can improve the diagnostic values of CWP.Keywords: coal workers’ pneumoconiosis, biomarker, osteopontin, Krebs von den Lungen-6, Syndecan-4, Gremlin-1
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