Proteomic Profile of Silicotic Rats Identifies PTPN2, VRK1, and B-Factor as New Biomarkers of Pneumoconiosis

Background: Pneumoconiosis is a chronic occupational lung disease caused by long-term inhalation of dust in the workplace. Identifying accurate and reliable biomarkers would enable earlier detection before irreversible deteced radiology changes occurred in the lung. Methods: We created a rat model that closely approximates the exposure and development of pneumoconiosis in humans. iTRAQ coupled with LC-MS technology was used to screen differentially-expressed proteins and validate them with patient bronchopulmonary lavage fluid and serum samples to assess whether these differentially expressed proteins were appropriate biomarkers for the diagnosis of pneumoconiosis. Findings: Totally, 471 proteins were differentially expressed in the pneumoconiosis group compared to controls. Twenty proteins with increased expression levels and eight with decreased levels exhibited a ≥ 1.5 foldchange relative to controls. We next determined whether similar changes in protein expression were detectable in human bronchoalveolar lavage fluid and serum. The levels of PTPN2, VRK1 and factor B were significantly higher in pneumoconiosis patients. The highest area under the curve(AUC) and diagnostic accuracy was the combined diagnosis of all three proteins. Interpretation: We found PTPN2, factor B, and VRK1 could be predictive biomarkers for pneumoconiosis. The three-factor combined diagnosis was found to be the most efficient for early diagnosis. Funding Statement: This work was supported by the precision medicine projects under the national key research and development programme of China (No. 2016YFC0900605); the Hebei Medical Science Research Foundation (No. 20190108); The Science and Technology Foundation of Tangshan (No. 18130206a); Postgraduate Innovation Foundation of North China University of Technology (No. 2017B20). Declaration of Interests: The authors declare that they have no conflicts interest. Ethics Approval Statement: Animal studies were performed with a protocol approved by the Institutional Animal Care and Use Committee of the North China University of Science and Technology, Tangshan, China (No. LX201868), all animals were carefully handled in compliance with the guidelines. All participants provided written informed consent, including consent to provide bronchopulmonary lavage fluid and serum to test for biomarkers predictive of pneumoconiosis, and studies carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. All studies were approved by the Ethics Committee of North China University of Science and Technology, Tangshan, China (No.2018021).