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

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:

• coal workers’ pneumoconiosis
• biomarker
• osteopontin
• Krebs von den Lungen-6
• Syndecan-4
• Gremlin-1

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval

This study was approved by the Ethics Committee of the China-Japan Friendship Hospital (NO. 2017-25-1) and the Ethics Committee of the Sinopharm Tongmei General Hospital (NO.201902).

Acknowledgments

The authors thank all miner workers who enrolled in our study.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

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.