title: Preliminary characterizations of a serum biomarker for sarcoidosis by comparative proteomic approach with tandem-mass spectrometry in ethnic Han Chinese patients.
abstract: BACKGROUND
  The diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis.
  
  
  METHODS
  Serum samples were collected from patients with sarcoidosis (n = 37), and compared to those from patients with tuberculosis (n = 20), other pulmonary diseases (n = 20), and healthy volunteers (n = 20) for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA) was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue.
  
  
  RESULTS
  An unique protein peak of M/Z 3,210 Daltons (Da) was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122) of serum amyloid A (SAA). ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p < 0.05). The cutoff for serum SAA concentration determined by ROC analysis was 101.98 ng/ml, with the sensitivity and specificity of 96.3% and 52.5%, respectively. Immunohistochemical staining showed that the SAA depositions in lung tissue of the sarcoidosis patients were also significantly more intense than in non-sarcoid lung tissue (p < 0.05).
  
  
  CONCLUSIONS
  This is the first study to investigate serum protein markers in Chinese subjects with sarcoidosis. This study shows that the serum SAA expression profiles were different between the sarcoidosis and non-sarcoidosis groups. SAA may be a potential serum biomarker for ruling-out the diagnosis of sarcoidosis in Chinese subjects.
authors: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
authors: Yuan
authors: Y
authors: Zhang
authors: Xianqiu
authors: X
authors: Chen
authors: Yang
authors: Y
authors: Hu
authors: Shanshan
authors: S
authors: Du
authors: Li
authors: L
authors: Shen
authors: Yifan
authors: Y
authors: He
authors: Yuxuan
authors: Y
authors: Zhang
authors: Xia
authors: X
authors: Zhang
authors: Huiping
authors: H
authors: Li
authors: Rex C
authors: RC
authors: Yung
mesh_terms: D044466:Asian People; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000208:ethnology; D008175:Lung Neoplasms / Q000097:blood / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000208:ethnology; D012372:ROC Curve; D015203:Reproducibility of Results; D017565:Sarcoidosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology*; D000685:Serum Amyloid A Protein / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000208:ethnology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D000685:Serum Amyloid A Protein
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