Distinct metabolic features in the plasma of patients with silicosis and dust-exposed workers in China: a case\u2013control study

Changjiang Xue,Qiao Ye,Jing Ma,Na Wu,Yali Fan

doi:10.1186/s12890-021-01462-1

Changjiang Xue, Qiao Ye + Show 3 more

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https://doi.org/10.1186/s12890-021-01462-1

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Abstract

BackgroundSilicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies.MethodsPatients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case–control study. The metabolomics analyses by ultra-high performance liquid chromatography-mass spectrometry were conducted. Distinct metabolic features (DMFs) were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored.ResultsTwenty-nine DMFs and 9 DMFs were detected and had the same trend in the pilot study and the validation study in the plasma of the DEW and silicosis groups, respectively. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. l-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis.ConclusionsDistinct metabolic features in the plasma of DEWs and the patients with silicosis were found to be different. Sphingolipid metabolism and arginine and proline metabolism were identified as the major metabolic pathway in the DEW and silicosis groups, respectively. l-arginine and kynurenine were correlated with the severity of silicosis.

Highlights

Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust
To identify the distinct metabolic features (DMFs) in silicosis, we evaluated the metabolic profiles in the plasma of patients with silicosis compared with dust-exposed workers without silicosis and healthy controls using pilot and validation metabolomics studies
Principal component analysis (PCA) and OPLS‐DA In this study, the differentially regulated plasma metabolites in the patients with silicosis, Dust-exposed worker (DEW) and healthy controls were searched by nontargeted metabolic profiling using UHPLC-Mass spectrometry (MS), and PCA, using the unsupervised model, was performed to reveal the differences in the metabolic profiles of samples among the groups

Summary

Introduction

Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. Silicosis is a progressive pneumoconiosis characterized by nodular interstitial fibrosis following exposure. The repeated process of phagocytosis, necrosis and rephagocytosis of the cells induces inflammation and activation of the reactive oxygen species system, which is associated with pulmonary interstitial fibrosis [6,7,8]. Our previous study showed that serum Krebs von den Lungen 6, surfactant protein D and matrix metalloproteinase-2 were potential biomarkers for diagnosing and monitoring silicosis [12]. Many metabolites are involved in the pathogenesis of silicosis and may play a predictive role in the diagnosis and severity of the disease. Research has suggested that cholesterol oxidation can be used as an important marker and lipid metabolism is affected and oxidative lipid damage is triggered in silicosis [13]

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