(12) United States Patent (10) Patent No.: US 7,972,785 B2 Hsieh Et Al
Total Page:16
File Type:pdf, Size:1020Kb
US00797 2785B2 (12) United States Patent (10) Patent No.: US 7,972,785 B2 Hsieh et al. (45) Date of Patent: Jul. 5, 2011 (54) BIOMARKERS FOR LIVER FIBROTIC Yi-Chao, Hsu, et al., “Increases in fibrosis-related gene transcripts in INJURY livers of dimethylnitrosamine-intoxicated rats.” J. Biomed Sci. 11:408-417 (2004). Shackel, Nicholas A. et al., “Gene array analysis and the liver.” (75) Inventors: Hui-Chu Hsieh, Changhua (TW); Hepatology, 36(6):1313-1325 (2002). Tzu-Ling Tseng, Chiayi (TW); Li-Jen Utsunomiya, Tohru, et al., “A gene-expression signature can quantify Su, Chiayi (TW); Chi-Ying Huang, the degree of hepatic fibrosis in the rat.” Journal of Hepatology, 41:399-406 (2004). Taipei (TW); Shih-Lan Hsu, Taipei Imaoka, Susumu, et al., “Localization of rat cytochrome P450 in (TW) various tissues and comparison of arachidonic acid metabolism by rat P450 with that by human P450 orthologs.” Drug Metab. (73) Assignees: Industrial Technology Research Pharmacokinet, 2006)478-484 (2005). Institute (ITRI), Hsinchu (TW); Wong, V. S., et al., "Serum hyaluronic acid is a useful marker of liver National Health Research Institutes fibrosis in chronic hepatitis C virus infection.” Journal of viral Hepa titis, 5:187-192 (1998). (NHRI), Miaoli County (TW) Ala-Kokko, L., et al., “Gene expression of type I, III and IV collagens in hepatic fibrosis induced by dimethylnitrosamine in the rat.” (*) Notice: Subject to any disclaimer, the term of this Biochem. J. 244:75-79 (1987). patent is extended or adjusted under 35 Arthur, M.J.P. et al., “Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis,” J. Gastroenterol. Hepatol. 13 U.S.C. 154(b) by 326 days. (Suppl.):S33-38 (1998). Bataller, R. and Brenner, D.A., “Liver fibrosis.' J. Clin. Invest. (21) Appl. No.: 11/656,389 115(2):209-218 (2005). Bauer, M. and Schuppan, D., “TGFB1 in liver fibrosis: time to change (22) Filed: Jan. 23, 2007 paradigms?.” FEBS Letts. 502:1-3 (2001). Benyon, R.C. and Arthur, M.J., “Extracellular matrix degradation (65) Prior Publication Data and the role of hepatic stellate cells.” Semin. Liver Dis. 21(3):373-84 (2001). US 2007/O184476A1 Aug. 9, 2007 Day, C.P. “Non-alcoholic steatohepatitis (NASH): where are we now and where are we going?” Gut 50:585-588 (2002). DeSouza, L., et al., “Search for cancer markers from endometrial Related U.S. Application Data tissues using differentially labeled tags iTRAQ and cICAT with mul (60) Provisional application No. 60/761,959, filed on Jan. tidimensional liquid chromatography and tandem mass spectrom etry,” J. Proteome Res.4(2):377-386 (2005). 24, 2006. Dooley, S., et al., “Transforming growth factor f3 signal transduction in hepatic stellate cells via Smad2/3 phosphorylation, a pathway that (51) Int. Cl. is abrogated during in vitro progression to myofibroblasts. TGFB CI2O I/68 (2006.01) signal transduction during transdifferentiation of hepatic stellate GOIN33/53 (2006.01) cells.” FEBS Letts. 502:4-10 (2001). Friedman, S.L., “Liver fibrosis—from bench to bedside.” J. Hepatol. (52) U.S. Cl. ........................................... 435/6: 435/7.92 38 (Suppl. 1):S38-53 (2003). (58) Field of Classification Search ........................ None Friedman, S.L., “Molecular regulation of hepatic fibrosis, an inte See application file for complete search history. grated cellular response to tissue injury.” J. Biol. Chem. 275(4):2247 2250 (2000). (56) References Cited Friedman, S.L., “Seminars in medicine of the Beth Israel Hospital, Boston: The cellular basis of hepatic fibrosis—Mechanisms and treatment strategies.” N. Engl. J. Med. 328(25): 1828-1835 (1993). U.S. PATENT DOCUMENTS George, J., et al., “Dimethylnitrosamine-induced liver injury in rats: 6,156,501 A 12/2000 McGallet al. the early deposition of collagen.” Toxicol. 156: 129-138 (2001). 2006/0246489 A1* 11/2006 Svetlov et al. .................... 435/6 Gressner, A.M., et al., “Roles of TGF-B in hepatic fibrosis.” Front. Biosci. 7:d793-807 (2002). FOREIGN PATENT DOCUMENTS EP 1 150 123 A1 10, 2001 (Continued) OTHER PUBLICATIONS Primary Examiner — Sharon Wen (74) Attorney, Agent, or Firm — Finnegan, Henderson, The Merck Manuals Online Medical Library, online). Whitehouse Farabow, Garrett & Dunner LLP Station, NJ: Merck Research Laboratories, 2007. retrieved on Apr. 7, 2009). Retrieved from the Internet: < URL: http://www.merck.com/ (57) ABSTRACT mmpe/print/sec()3/ch026/ch026b.html>. Fibrosis, pp. 1-3.* The present invention provides a method for detecting liver Afdhal Clinical Chemistry 2004, 50: 1299-1300.* fibrotic injury, including fibrosis and/or cirrhosis, by assaying Bast, Jr. et al. Clinical Cancer Research, 2005, vol. 11, pp. 6103 6108. biological samples for differential expression of at least one LaBaer et al. Journal of Proteome Research, 2005, vol. 4, pp. 1053 gene encoding a protein chosen from SEQID NO: 1-SEQID 1059. NO: 63 and human orthologs thereof, wherein differential Baker Nature Biotechnology, 2005, vol. 23, pp. 297-304.* expression of at least one gene Suggests the presence of liver Honda et al. Journal of Autoimmunity 2005, 25:133-140.* fibrosis or cirrhosis. The invention also provides a kit con Ala-Kokko, Leena, et al., “Gene expression of type I, III and IV taining nucleic acid probes or antibodies for detecting liver collagens in hepatic fibrosis induced by dimethylnitrosamine in the fibrosis and/or cirrhosis by assaying the differential expres rat.” Biochem. J., 244:75-79 (1987). sion of proteins encoded by SEQID NO: 1-SEQ ID NO: 63 Rosenberg, William M. C., et al., "Serum markers detect the presence and human orthologs thereof. of liver fibrosis: A cohort study.” Gastroenterology, 127:1704-1713 (2004). 3 Claims, 8 Drawing Sheets US 7,972,785 B2 Page 2 OTHER PUBLICATIONS Mirsalis, J.C., and Butterworth, B.E., "Detection of unscheduled Haggerty, H.G. and Holsapple, M.P., “Role of metabolism in DNA synthesis in hepatocytes isolated from rats treated with dimethylnitrosamine-induced immunosuppression: a review.” genotoxic agents: an in vivo invitro assay for potential carcinogens and mutagens.” Carcinogenesis 1:621-624 (1980). Toxicol. 63:1-23 (1990). Morgan, C.L., Newman, D.J., Burrin, J.M., and Price, C.P. "The Hayaska, A. and Saisho, H., "Serum markers as tools to monitor liver matrix effects on kinetic rate constants of antibody-antigen interac fibrosis.” Digestion 59:381-384 (1998). tions reflect solvent viscosity.” J. Immunol. Meth. 217:51-60 (1998). Hernández-Munoz, R., et al., “Adenosine reverses a preestablished Neubauer, K., et al., "Accumulation and cellular localization of CC1-induced micronodular cirrhosis through enhancing col fibrinogen/fibrin during short-term and long-term rat liver injury.” lagenolytic activity and stimulating hepatocyte cell proliferation in Gastroenterol. 108:1124-1135 (1995). rats.” Hepatol. 34:677-687 (2001). Nielsen, P.E., et al., “Sequence-selective recognition of DNA by Hippo. Y., et al., “Global gene expression analysis of gastric cancer by Strand displacement with a thymine-substituted polyamide.” Science. 254(5037): 1497-1500 (1991). oligonucleotide microarrays.” Cancer Res.62:233-240 (2002). Okita, K., et al., “Current strategies for chemoprevention of Iizuka, N., et al., “Differential gene expression in distinct virologic hepatocellular carcinoma.” Oncology 62 (Suppl. 1):24-28 (2002). types of hepatocellular carcinoma: association with liver cirrhosis.” Sambrook et al., Molecular Cloning. A Laboratory Manual, vol. 3, Oncogene 22:3007-3014 (2003). pp. A8.40-A8.45 and A8.52-A8.55 (3d ed., Cold Spring Harbor Iredale, J.P., “Cirrhosis: new research provides a basis for rational Laboratory Press, Cold Spring Harbor, New York 2001). and targeted treatments.” BMJ 327:143-147 (2003). Schuppan, D., et al., “Hepatitis C and liver fibrosis.” Cell Death Iredale, J.P. "Tissue inhibitors of metalloproteinases in liver fibro Differ. 10:S59-67 (2003). sis.” Int. J. Biochem. Cell Biol. 29(1):43-54 (1997). Seth, D., et al., “Gene expression profiling of alcoholic liver disease Ishak, K., et al., “Histological grading and staging of chronic hepa in the baboon (Papio hamadryas) and human liver.” Am. J. Pathol. titis.” J. Hepatol. 22:696-699 (1995). 163(6):2303-2317 (2003). Jézequel, A.M., et al., "A morphological study of the early stages of Strauss, W.M., "Hybridization With Radioactive Probes.” in Current hepatic fibrosis induced by low doses of dimethylnitrosamine in the Protocols in Molecular Biology 6.3.1-6.3.6. (John Wiley & Sons, rat.” J. Hepatol. 5:174-181 (1987). N.Y. 2000). Ji, J., et al., “Comprehensive analysis of the gene expression profiles Waring, J.F., et al., “Microarray analysis of hepatotoxins in vitro in human gastric cancer cell lines.” Oncogene 21:6549-6556 (2002). reveals a correlation between gene expression profiles and mecha Knodell, R.G., et al., “Formulation and application of a numerical nisms of toxicity.” Toxicol. Letts. 120:359-368 (2001). scoring system for assessing histological activity in asymptomatic Waring, J.F., et al., "Clustering of hepatotoxins based on mechanism chronic active hepatitis.” Hepatol. 1(5):431-435 (1981). of toxicity using gene expression profiles. Toxicol. Appl. Pharmacol. López-De León, A. and Rojkind, M., “A simple micromethod for 175:28-42 (2001). collagen and total protein determination in formalin-fixed paraffin Wright, M.E., et al., “Mass spectrometry-based expression profiling embedded sections.”.J. Histochem. Cytochem. 33(8):737-743 (1985). of clinical prostate cancer.” Mol. Cell. Proteomics 44:545-554 Marvanová, M., et al., “Microarray analysis of nonhuman primates: (2005). validation of experimental models in neurological disorders.” FASEB Zhuang, G., et al., “Measurement of Association Rate Constant of J. 17:929-931 (2003). Antibody-Antigen Interactions in Solution Based on Enzyme-Linked MaZZocca, A., et al., “Expression of transmembrane 4 Superfamily Immunosorbent Assay.” J. Biosci. Bioeng. 92(4):330-336 (2001). (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration.” J.