Serum protein isoform profiles indicate the progression of hepatitis C virus-induced liver diseases

Sugimoto,Kazushi; Shiraki,Katsuya; Takei,Yoshiyuki; Ito,Masaaki; Nobori,Tsutomu; Suzuki,Hideaki; Dissanayaka,Santha  K.; Meno,Kohji; Asashima,Makoto; Uchida,Kazuhiko

doi:10.3892/ijmm.2013.1267

Serum protein isoform profiles indicate the progression of hepatitis C virus-induced liver diseases

Authors:
- Kazushi Sugimoto
- Katsuya Shiraki
- Yoshiyuki Takei
- Masaaki Ito
- Tsutomu Nobori
- Hideaki Suzuki
- Santha K. Dissanayaka
- Kohji Meno
- Makoto Asashima
- Kazuhiko Uchida
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Affiliations: Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Japan, First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan, Department of Gastroenterology, Mie University School of Medicine, Tsu, Japan, Tsukuba Industrial Liaison and Cooperative Research Center, University of Tsukuba, Tsukuba, Japan, Research Center for Stem Cell Engineering National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
Published online on: February 4, 2013 https://doi.org/10.3892/ijmm.2013.1267
Pages: 943-950

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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.

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1	Niederau C, Lange S, Heintges T, Erhardt A, Buschkamp M, Hurter D, Nawrocki M, Kruska L, Hensel F, Petry W and Häussinger D: Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 28:1687–1695. 1998. View Article : Google Scholar : PubMed/NCBI
2	Friedman SL: Liver fibrosis - from bench to bedside. J Hepatol. 38(Suppl 1): S38–S53. 2003. View Article : Google Scholar
3	Cadranel JF, Rufat P and Degos F: Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology. 32:477–481. 2000. View Article : Google Scholar : PubMed/NCBI
4	Poynard T, Ratziu V and Bedossa P: Appropriateness of liver biopsy. Can J Gastroenterol. 14:543–548. 2000.PubMed/NCBI
5	He QY, Cheung YH, Leung SY, Yuen ST, Chu KM and Chiu JF: Diverse proteomic alterations in gastric adenocarcinoma. Proteomics. 4:3276–3287. 2004. View Article : Google Scholar : PubMed/NCBI
6	Qi Y, Chiu JF, Wang L, Kwong DL and He QY: Comparative proteomic analysis of esophageal squamous cell carcinoma. Proteomics. 5:2960–2971. 2005. View Article : Google Scholar : PubMed/NCBI
7	Finehout EJ, Franck Z and Lee KH: Complement protein isoforms in CSF as possible biomarkers for neurodegenerative disease. Dis Markers. 21:93–101. 2005. View Article : Google Scholar : PubMed/NCBI
8	Kanninen K, Goldsteins G, Auriola S, Alafuzoff I and Koistinaho J: Glycosylation changes in Alzheimer’s disease as revealed by a proteomic approach. Neurosci Lett. 367:235–240. 2004.
9	Zanusso G, Righetti PG, Ferrari S, Terrin L, Farinazzo A, Cardone F, Pocchiari M, Rizzuto N and Monaco S: Two-dimensional mapping of three phenotype-associated isoforms of the prion protein in sporadic Creutzfeldt-Jakob disease. Electrophoresis. 23:347–355. 2002. View Article : Google Scholar : PubMed/NCBI
10	He QY, Lau GK, Zhou Y, Yuen ST, Lin MC, Kung HF and Chiu JF: Serum biomarkers of hepatitis B virus infected liver inflammation: a proteomic study. Proteomics. 3:666–674. 2003. View Article : Google Scholar : PubMed/NCBI
11	Steel LF, Shumpert D, Trotter M, Seeholzer SH, Evans AA, London WT, Dwek R and Block TM: A strategy for the comparative analysis of serum proteomes for the discovery of biomarkers for hepatocellular carcinoma. Proteomics. 3:601–609. 2003. View Article : Google Scholar : PubMed/NCBI
12	Burgess-Cassler A, Johansen JJ and Kendrick NC: Two-dimensional gel analysis of serum apolipoprotein A-I isoforms: preliminary analysis suggests altered ratios in individuals with heart disease. Appl Theor Electrophor. 3:41–45. 1992.
13	Fuhrman MP, Charney P and Mueller CM: Hepatic proteins and nutrition assessment. J Am Diet Assoc. 104:1258–1264. 2004. View Article : Google Scholar : PubMed/NCBI
14	Tong L, Baskaran G, Jones MB, Rhee JK and Yarema KJ: Glycosylation changes as markers for the diagnosis and treatment of human disease. Biotechnol Genet Eng Rev. 20:199–244. 2003. View Article : Google Scholar : PubMed/NCBI
15	Gravel P, Walzer C, Aubry C, Balant LP, Yersin B, Hochstrasser DF and Guimon J: New alterations of serum glycoproteins in alcoholic and cirrhotic patients revealed by high resolution two-dimensional gel electrophoresis. Biochem Biophys Res Commun. 220:78–85. 1996. View Article : Google Scholar : PubMed/NCBI
16	Garner B, Merry AH, Royle L, Harvey DJ, Rudd PM and Thillet J: Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. J Biol Chem. 276:22200–22208. 2001. View Article : Google Scholar : PubMed/NCBI
17	He Z, Aristoteli LP, Kritharides L and Garner B: HPLC analysis of discrete haptoglobin isoform N-linked oligosaccharides following 2D-PAGE isolation. Biochem Biophys Res Commun. 343:496–503. 2006. View Article : Google Scholar : PubMed/NCBI
18	Nelsestuen GL, Zhang Y, Martinez MB, Key NS, Jilma B, Verneris M, Sinaiko A and Kasthuri RS: Plasma protein profiling: unique and stable features of individuals. Proteomics. 5:4012–4024. 2005. View Article : Google Scholar : PubMed/NCBI
19	Sahu A and Lambris JD: Structure and biology of complement protein C3, a connecting link between innate and acquired immunity. Immunol Rev. 180:35–48. 2001. View Article : Google Scholar : PubMed/NCBI
20	Lee IN, Chen CH, Sheu JC, Lee HS, Huang GT, Chen DS, Yu CY, Wen CL, Lu FJ and Chow LP: Identification of complement C3a as a candidate biomarker in human chronic hepatitis C and HCV-related hepatocellular carcinoma using a proteomics approach. Proteomics. 6:2865–2873. 2006. View Article : Google Scholar : PubMed/NCBI
21	Gangadharan B, Antrobus R, Dwek RA and Zitzmann N: Novel serum biomarker candidates for liver fibrosis in hepatitis C patients. Clin Chem. 53:1792–1799. 2007. View Article : Google Scholar : PubMed/NCBI
22	Citarella F, Felici A, Brouwer M, Wagstaff J, Fantoni A and Hack CE: Interleukin-6 downregulates factor XII production by human hepatoma cell line (HepG2). Blood. 90:1501–1507. 1997.PubMed/NCBI
23	Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y and Poynard T: Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 357:1069–1075. 2001. View Article : Google Scholar : PubMed/NCBI
24	Myers RP, De Torres M, Imbert-Bismut F, Ratziu V, Charlotte F and Poynard T: Biochemical markers of fibrosis in patients with chronic hepatitis C: a comparison with prothrombin time, platelet count, and age-platelet index. Dig Dis Sci. 48:146–153. 2003. View Article : Google Scholar : PubMed/NCBI
25	Rossi E, Adams L, Prins A, Bulsara M, de Boer B, Garas G, MacQuillan G, Seers D and Jeffrey G: Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Clin Chem. 49:450–454. 2003. View Article : Google Scholar : PubMed/NCBI
26	Vergnes L, Baroukh N, Lehy T, Moizo L, Bado A, Baralle M, Baralle FE, Zakin MM and Ochoa A: Human apolipoprotein A-IV reduces gastric acid secretion and diminishes ulcer formation in transgenic mice. FEBS Lett. 460:178–181. 1999. View Article : Google Scholar : PubMed/NCBI
27	Quilliot D, Walters E, Guerci B, Fruchart JC, Duriez P, Drouin P and Ziegler O: Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis. Metabolism. 50:1019–1024. 2001. View Article : Google Scholar : PubMed/NCBI
28	Miyata Y, Koga S and Ibayashi H: Alterations in plasma levels of apolipoprotein A-IV in various clinical entities. Gastroenterol Jpn. 21:479–485. 1986.PubMed/NCBI
29	Seishima M, Usui T, Naganawa S, Nishimura M, Moriwaki H, Muto Y and Noma A: Reduction of intestinal apo A-IV mRNA levels in the cirrhotic rat. J Gastroenterol Hepatol. 11:746–751. 1996. View Article : Google Scholar : PubMed/NCBI