title: Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B.
abstract: OBJECTIVE
  Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients.
  
  
  METHODS
  Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM).
  
  
  RESULTS
  21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn's index and serum DAK protein.
  
  
  CONCLUSIONS
  The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Xu
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Rui-Dan
authors.initials: RD
authors.lastname: Zheng
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Yuan
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Weng
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Wang
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Lun-Gen
authors.initials: LG
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D019540:Area Under Curve; D002853:Chromatography, Liquid; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007477:Ions; D008969:Molecular Sequence Data; D010455:Peptides / Q000097:blood* / Q000737:chemistry; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000097:blood* / Q000737:chemistry; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry
chemical_list: D007477:Ions; D010455:Peptides; D017853:Phosphotransferases (Alcohol Group Acceptor); C023132:glycerone kinase