title: Potential proteomic biomarkers in assessing liver fibrosis using SELDI-TOF MS.
abstract: OBJECTIVE
  The accurate assessment of the severity of liver fibrosis is of paramount importance in determining treatment strategies, response to treatment and prognosis in patients with chronic liver disease. The aim of this study was to investigate potential proteomic biomarkers for assessing stages of hepatic fibrosis.
  
  
  METHODS
  Serum samples of 83 patients with chronic liver disease (using METAVIR index, 17 F0, 30 F1, 6 F2, 9 F3, and 21 F4 patients) and 29 healthy controls were analyzed using surface-enhanced laser desorption/ionization time-of- flight mass spectrometry on IMAC30 ProteinChip arrays. Discriminatory peaks between groups were identified using Mann-Whitney U non-parametric test. Comparison of mild (F0, F1) and severe fibrosis (F2, F3, F4) was performed using tree classification (cross-validation) with the Biomarker Patterns Software, version 5.0 (Ciphergen Biosystems, US).
  
  
  RESULTS
  No statistically significant discriminatory peak was evident between F0, F1 and F2 fibrosis. More than 30 peaks were found to be discriminatory between patients with cirrhosis (F4) and all other stages of liver fibrosis, including F2 and F3. Six surface-enhanced laser desorption/ionization proteomic features were found to be discriminative for mild (F0, F1) vs. advanced (F2, F3, F4) fibrosis (AUROC ≥0.8, p<0.05, Mann-Whitney test). The decision tree (m/z 4280, 10453 and 6376) yielded a sensitivity of 83.3% (30/36), a specificity of 85.1% (40/47), a positive predictive value of 81.1%, and a negative predictive value of 86.9%, with an AUROC of 0.94.
  
  
  CONCLUSIONS
  The results of this study revealed discriminatory peaks between the protein profiles of patients with cirrhosis and other stages of liver fibrosis. Potential proteomic biomarkers can be notably determined for discriminating mild and advanced fibrosis using surface-enhanced laser desorption/ionization time-of- flight mass spectrometry.
authors.forename: Senem Ceren
authors.initials: SC
authors.lastname: Karatayli
authors.forename: S Gökçe
authors.initials: SG
authors.lastname: Alagöz
authors.forename: Dilşa
authors.initials: D
authors.lastname: Mizrak
authors.forename: Müyesser
authors.initials: M
authors.lastname: Sayki
authors.forename: Muhip
authors.initials: M
authors.lastname: Ozkan
authors.forename: Berna
authors.initials: B
authors.lastname: Savaş
authors.forename: Esra
authors.initials: E
authors.lastname: Erden
authors.forename: Kubilay
authors.initials: K
authors.lastname: Cinar
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idılman
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: A Mithat
authors.initials: AM
authors.lastname: Bozdayi
mesh_terms: D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D003663:Decision Trees; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000145:classification*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D040901:Proteomics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D001798:Blood Proteins