Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study

Zhifei Hou; Xinran Zhang; Yong Gao; Jing Geng; Yu Jiang; Huaping Dai; Chen Wang

doi:10.2147/PGPM.S409644

Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study

Pharmgenomics Pers Med. 2023 Jun 1:16:537-549. doi: 10.2147/PGPM.S409644. eCollection 2023.

Authors

Zhifei Hou^{1

2}, Xinran Zhang³, Yong Gao⁴, Jing Geng², Yu Jiang⁵, Huaping Dai^{1

2}, Chen Wang^{1

2}

Affiliations

¹ Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
² Department 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.
³ Department 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.
⁴ Department of Pulmonary and Critical Care Medicine, Sinopharm Tongmei General Hospital, Datong, Shanxi Province, People's Republic of China.
⁵ Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.

Abstract

Background: 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: Gremlin-1; Krebs von den Lungen-6; Syndecan-4; biomarker; coal workers’ pneumoconiosis; osteopontin.

Grants and funding

This work was supported by Grants from National Key Technologies R & D Program Precision China (No.: 2021YFC2500700, 2016YFC0901101) and CAMS Innovation Fund for Medical Science (CIFMS), 2021-I2M-1-049.