Utilizing 2-DE And MALDI-TOF MS/MS To Screen Differentially Expressed Serum Proteins Of Silicosis

Silicosis, an occupational disease characterized by extracellular matrix (ECM) deposition in lung interstitial, is caused by long-time inhalation of free SiO2 dust. It is one of the most common and detrimental occupational diseases with high mortality. The pathogenesis is still not clear now. The government of China had repored that the number of new pneumoconiosis is 9173, which accounts for 75.1% of the total occupational disease cases in 2005. Half of pneumoconiosis is silicosis, which causes more than nine billion RMB losses directly every year.The rapid progress of silicosis poses a challenge to prevent and manage this particular disease. Under such condition, an early intervention may slow down the progress of silicosis. With the rapid development of advanced techniques in recent years, proteomics provides a new platform for screening specific biomarkers of diseases and studying the pathogenesis. Since silica particles activate macrophages and fibroblasts of the lung, which lead to the production of reactive oxygen species, reactive nitrogen species, cytokines and chemokines, and inflammation, granulomatous and fibrotic changes in the lung, it offers the possibility of serum differential proteomics study for silicosis. In this study, 2-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS) were applied to reveal the differential expressions of serum proteins between silicosis population and healthy subjects to explore specific serum biomarkers for the early diagnosis of silicosis.ObjectiveTo establish the profile of differentially expressed serum proteins in patients with silicosis, to seek latent biomarkers for early diagnosis and study the pathogenesis of this disease.MethodsThirty healthy workers without silica exposure history were chosen as control and ninety silica exposure workers without other lung diseases were classified into 0, 0+ and I phase of silicosis according to the national diagnostic standard (GBZ70-2002, China) of pneumonoconiosis, respectively. Blood samples were collected simultaneously with investigation of the general information of the subjects and serum samples were analyzed by 2-DE and MALDI-TOF-MS/MS to screen differentially expressed serum proteins of silicosis patients.ResultsComplement C4, leucine-rich alpha-2-glycoprotein and alpha-1– antitrypsin were significantly up regulated in 0+ group (P <0.01), but lower in other groups. Inversely, serotransferrin was significantly low expressed only in 0~+ group (P <0.01). Glutathione peroxidase, tetranectin, apolipoprotein A-I and transthyretin were equally expressed in sera of the control and 0 group, but down regulated with the fibrosis progressing of silicosis.ConclusionsComplement C4, leucine-rich alpha-2-glycoprotein, alpha-1-antitrypsin, serotransferrin may play an important role in cytolysis and inflammation at the early stage of silicosis and have the potential value for early diagnosis of silicosis. Glutathione peroxidase, tetranectin, apolipoprotein A-I and transthyretin are down regulated with the progressing of fibrosis, such tendency indicates that there may exist some latent correlation.The results need to be validated by other biological methods such as wester-blot or ELISA individually. Yet, further studies should be done to reveal the definite roles in the pathogenesis of silicosis.