title: Serum protein isoform profiles indicate the progression of hepatitis C virus-induced liver diseases.
abstract: Biomarkers that enable an accurate diagnosis of hepatitis C virus (HCV)-induced liver diseases are necessary to prevent subsequent patient morbidity and suffering from the onset of hepatocellular carcinoma (HCC). In particular, the identification of novel biomarkers for liver cirrhosis (LC) will be an important new diagnostic tool since more than 70% of HCV-induced LCs are destined to develop into HCC. In our current study, we performed a search for new serological protein biomarkers of HCV-induced chronic hepatitis (CH), LC and HCC, using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The disease-affected spots were subsequently identified as isoforms of protein components of haptoglobin, transthyretin, the haptoglobin α-chain and apolipoprotein A-IV (apo A-IV), and in specific instances were significantly reduced in LC (p<0.001) and HCC (p<0.01), compared with CH patients. We further examined these isoforms by receiver operating characteristics (ROC) curve analysis and found that they showed high area under ROC curve (AUC) values of more than 0.8 between CH and LC, suggesting that they are appropriate markers that could be utilized to discriminate LC from CH. In conclusion, protein variants in serum that arise as a result of post-translational modifications prove to be useful biomarkers for the accurate diagnosis of specific liver diseases.
authors: Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Japan. kazushi@clin.medic.mie-u.ac.jp
authors: Kazushi
authors: K
authors: Sugimoto
authors: Katsuya
authors: K
authors: Shiraki
authors: Yoshiyuki
authors: Y
authors: Takei
authors: Masaaki
authors: M
authors: Ito
authors: Tsutomu
authors: T
authors: Nobori
authors: Hideaki
authors: H
authors: Suzuki
authors: Santha K
authors: SK
authors: Dissanayaka
authors: Kohji
authors: K
authors: Meno
authors: Makoto
authors: M
authors: Asashima
authors: Kazuhiko
authors: K
authors: Uchida
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D001798:Blood Proteins / Q000032:analysis / Q000737:chemistry; D016022:Case-Control Studies; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000209:etiology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000097:blood / Q000737:chemistry; D020543:Proteome / Q000032:analysis / Q000737:chemistry; D040901:Proteomics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020033:Protein Isoforms; D020543:Proteome