title: Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma.
abstract: Haptoglobin is a liver-secreted glycoprotein with four N-glycosylation sites. Its glycosylation was reported to change in several cancer diseases, which prompted us to examine site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. To this end, we have used two-dimensional separation composed of hydrophilic interaction and nano-reverse phase chromatography coupled to QTOF mass spectrometry of the enriched glycopeptides. Our results show increased fucosylation of haptoglobin in liver disease with up to six fucoses associated with specific glycoforms of one glycopeptide. Structural analysis using exoglycosidase treatment and MALDI-MS/MS of detached permethylated glycans led to the identification of Lewis Y-type structures observed particularly in the pooled hepatocellular carcinoma sample. To confirm the increase of the Lewis Y structures observed by LC-MS, we have used immunoaffinity detection with Lewis Y-specific antibodies. The presence of multiply fucosylated Lewis Y glycoforms of haptoglobin in the disease context could have important functional implications.
authors: Department of Oncology, Georgetown University, Washington, DC 20057, USA.
authors: Petr
authors: P
authors: Pompach
authors: Zuzana
authors: Z
authors: Brnakova
authors: Miloslav
authors: M
authors: Sanda
authors: Jing
authors: J
authors: Wu
authors: Nathan
authors: N
authors: Edwards
authors: Radoslav
authors: R
authors: Goldman
mesh_terms: D000595:Amino Acid Sequence; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016022:Case-Control Studies; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006242:Haptoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational
chemical_list: C485359:HP protein, human; D006242:Haptoglobins; D005643:Fucose
references: Anal Chem. 2010 Dec 15;82(24):10208-15
references: 21073175
references: Glycoconj J. 1991 Oct;8(5):390-9
references: 1841681
references: Int J Cancer. 2008 May 15;122(10):2301-9
references: 18214858
references: PLoS One. 2011;6(12):e29011
references: 22205989
references: J Proteome Res. 2012 Mar 2;11(3):1728-40
references: 22239659
references: Mol Cell Proteomics. 2012 Jan;11(1):M111.008730
references: 21986992
references: Glycobiology. 2007 Dec;17(12):1344-56
references: 17884841
references: Glycobiology. 2005 Jan;15(1):87-100
references: 15317738
references: Cancer Res. 1993 Nov 15;53(22):5419-23
references: 7693340
references: Int J Cancer. 2006 Jun 1;118(11):2803-8
references: 16385567
references: Proteomics. 2008 Aug;8(16):3257-62
references: 18646007
references: Eur J Clin Chem Clin Biochem. 1997 Sep;35(9):647-54
references: 9352226
references: Mol Cell Proteomics. 2009 May;8(5):986-94
references: 19181623
references: J Virol. 2008 Feb;82(3):1259-70
references: 18045939
references: Cancer Epidemiol Biomarkers Prev. 2012 Jun;21(6):925-33
references: 22490318
references: Anal Chem. 2010 Feb 1;82(3):1073-81
references: 20058878
references: Annu Rev Biochem. 1985;54:631-64
references: 3896128
references: J Proteomics. 2012 Apr 3;75(7):2216-24
references: 22326963
references: Anal Biochem. 2008 May 1;376(1):1-12
references: 18194658
references: Proc Soc Exp Biol Med. 1968 Jan;127(1):52-9
references: 4966982
references: Anal Chem. 2011 Mar 15;83(6):2029-37
references: 21338062
references: Nature. 2012 Sep 20;489(7416):456-9
references: 22922649
references: Proteomics Clin Appl. 2010 Apr;4(4):372-8
references: 21137057
references: Mol Cell Proteomics. 2012 Jul;11(7):M111.015792
references: 22393262
references: Clin Proteomics. 2011 Jun 03;8(1):7
references: 21906357
references: Clin Cancer Res. 2009 Mar 1;15(5):1808-13
references: 19223512
references: PLoS One. 2010 Aug 25;5(8):e12419
references: 20811639
references: Int J Oncol. 2010 May;36(5):1291-7
references: 20372805
references: Acta Biochim Biophys Sin (Shanghai). 2011 Jul;43(7):528-34
references: 21606158
references: Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G833-42
references: 21292995
references: Am J Gastroenterol. 2007 Oct;102(10):2196-205
references: 17617202
references: J Chromatogr A. 2011 Dec 9;1218(49):8890-6
references: 21530976
references: Nat Methods. 2009 Nov;6(11):809-11
references: 19838169
references: Eur J Biochem. 1989 Sep 15;184(2):405-13
references: 2551687
references: J Gastroenterol Hepatol. 1998 Jun;13(6):610-9
references: 9715405
references: J Hepatol. 2009 Mar;50(3):592-603
references: 19157620
references: Alcohol Clin Exp Res. 1994 Apr;18(2):392-7
references: 8048744
references: Gastroenterology. 1990 Aug;99(2):508-18
references: 1694805
references: Science. 2011 Sep 23;333(6050):1761-4
references: 21852454
references: Annu Rev Biochem. 2008;77:521-55
references: 18518825
references: PLoS One. 2011;6(10):e26560
references: 22028908
references: FEBS J. 2008 Nov;275(22):5648-56
references: 18959750
references: J Proteome Res. 2011 May 6;10(5):2602-11
references: 21417406
references: Rapid Commun Mass Spectrom. 2006;20(11):1747-54
references: 16676317
references: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14294-9
references: 9405606
references: J Biol Chem. 2006 Oct 6;281(40):29797-806
references: 16899455
references: J Biol Chem. 2008 Jul 4;283(27):18601-11
references: 18467335
references: Electrophoresis. 2011 Jun;32(12):1422-32
references: 21692080
references: Int J Cancer. 2008 Jan 1;122(1):39-49
references: 17803183
references: Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1914-21
references: 19454616
references: Electrophoresis. 2009 Aug;30(15):2617-23
references: 19621379
references: Mol Cell Proteomics. 2013 May;12(5):1294-305
references: 23389048
references: Nature. 2001 Jan 11;409(6817):198-201
references: 11196644
references: Cell. 1985 Nov;43(1):287-95
references: 3000603
references: J Proteome Res. 2010 Jan;9(1):227-36
references: 19921957
references: Cancer. 1991 Jan 15;67(2):476-80
references: 1702350
references: Anal Chem. 2010 Jun 15;82(12):5095-106
references: 20491449