title: Serum peptide pattern that differentially diagnoses hepatitis B virus-related hepatocellular carcinoma from liver cirrhosis.
abstract: BACKGROUND
  Although alpha-fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it is not sufficiently sensitive to differentiate HCC and liver cirrhosis (LC) caused by hepatitis B virus (HBV) infection.
  
  
  OBJECTIVE
  The aim is to discover novel noninvasive specific serum biomarkers for the differential diagnosis of HBV-related HCC and LC.
  
  
  METHODS
  With a highly optimized peptide extraction and matrix-assisted laser desorption/ionization time of flight/time of flight mass spectrometric approach, we investigated serum peptide profiles of 80 HCC and 67 LC patients. Three supervised machine learning methods were employed to construct classifiers. Receiver operator curves were plotted to evaluate the performance of classifiers.
  
  
  RESULTS
  With a support vector machine-based strategy, we picked nine peaks with m/z ratios of 819.49, 1076.14, 1341.72, 2551.44, 3156.44, 3812.88, 4184.26, 4465.92, and 4776.41 to construct the classifier. We proposed a novel method for distinguishing HCC from cirrhosis, based on a multilayer perceptron (MLP) method. We obtained a sensitivity of 90.0%, specificity of 79.4%, and overall accuracy of 85.1% on an independent test set. The combination of the MLP model and serum AFP level outperformed serum AFP marker alone in distinguishing HCC patients from LC patients. In this experience, sensitivity increased from 62.5% to 87.5%, and specificity increased from 79.4% to 88.2%.
  
  
  CONCLUSIONS
  Our results indicate that the MLP model is a novel and useful serum peptide pattern for distinguishing HCC and LC. The peptidome signature alone or together with serum AFP determination may be a more effective method for early diagnosis of HCC in patients with HBV-related LC.
authors.affiliation: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Si
authors.forename: Cheng-Jin
authors.initials: CJ
authors.lastname: Hu
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Li
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000209:etiology*; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D010455:Peptides / Q000097:blood*; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D010455:Peptides; D000509:alpha-Fetoproteins
keywords: differential diagnosis; hepatocellular carcinoma; liver cirrhosis; serum peptide