title: Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms.
abstract: OBJECTIVE
  Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis.
  
  
  METHODS
  We used a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of mucin (MUC)1, MUC5AC, MUC16, carcinoembryonic antigen, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (n=17), intraductal papillary mucinous neoplasms (n=15), serous cystadenomas (n=12), or pseudocysts (n=9), with confirmation of histologic diagnosis at surgical resection.
  
  
  RESULTS
  The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (mucinous cystic neoplasms+intraductal papillary mucinous neoplasms) from benign cystic lesions (serous cystadenomas+pseudocysts) with a 78% sensitivity at 80% specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87% at 86% specificity. These biomarkers performed better than cyst fluid carcinoembryonic antigen (37%/80% sensitivity/specificity).
  
  
  CONCLUSIONS
  These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Haab
authors.forename: Andrew
authors.initials: A
authors.lastname: Porter
authors.forename: Tingting
authors.initials: T
authors.lastname: Yue
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Scheiman
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Anderson
authors.forename: Dawn
authors.initials: D
authors.lastname: Barnes
authors.forename: C Max
authors.initials: CM
authors.lastname: Schmidt
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Diane M
authors.initials: DM
authors.lastname: Simeone
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D044963:Biopsy, Fine-Needle; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D020420:Cyst Fluid / Q000737:chemistry*; D003536:Cystadenocarcinoma / Q000737:chemistry; D018291:Cystadenoma, Mucinous / Q000737:chemistry; D018293:Cystadenoma, Serous / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016015:Logistic Models; D055271:Mucin 5AC / Q000032:analysis; D009077:Mucins / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D010192:Pancreatic Pseudocyst / Q000737:chemistry / Q000175:diagnosis; D040081:Protein Array Analysis; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins
references.citation: Int J Cancer. 2006 Jun 1;118(11):2803-8
references.pmid: 16385567
references.citation: Proteomics. 2008 Aug;8(16):3257-62
references.pmid: 18646007
references.citation: Int J Cancer. 1991 Jan 21;47(2):180-7
references.pmid: 1988363
references.citation: Clin Gastroenterol Hepatol. 2006 Jun;4(6):766-81; quiz 665
references.pmid: 16682259
references.citation: Am J Surg Pathol. 2004 Aug;28(8):977-87
references.pmid: 15252303
references.citation: Pancreas. 2007 May;34(4):466-9
references.pmid: 17446847
references.citation: Nat Rev Cancer. 2004 Jan;4(1):45-60
references.pmid: 14681689
references.citation: Gastrointest Endosc. 2009 May;69(6):1103-5
references.pmid: 19410042
references.citation: J Proteome Res. 2007 May;6(5):1864-74
references.pmid: 17428079
references.citation: J Gastrointest Surg. 2000 Nov-Dec;4(6):567-79
references.pmid: 11307091
references.citation: J Biol Chem. 1997 Sep 26;272(39):24198-202
references.pmid: 9305871
references.citation: Int J Cancer. 1997 Jun 20;74(3):286-90
references.pmid: 9221806
references.citation: J Gastrointest Surg. 2004 Jul-Aug;8(5):569-74
references.pmid: 15239993
references.citation: Mod Pathol. 2007 Feb;20 Suppl 1:S71-93
references.pmid: 17486054
references.citation: J Mol Med (Berl). 1997 Aug;75(8):594-602
references.pmid: 9297627
references.citation: EMBO Rep. 2006 Jun;7(6):599-604
references.pmid: 16741504
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2897-902
references.pmid: 16782929
references.citation: Br J Cancer. 2004 Nov 1;91(9):1633-8
references.pmid: 15494719
references.citation: Pancreatology. 2007;7(1):9-19
references.pmid: 17449961
references.citation: Nat Methods. 2007 May;4(5):437-44
references.pmid: 17417647
references.citation: Br J Cancer. 1988 Nov;58(5):589-93
references.pmid: 3265332
references.citation: Biochim Biophys Acta. 1999 Dec 6;1473(1):21-34
references.pmid: 10580127
references.citation: Br J Cancer. 1991 Aug;64(2):386-90
references.pmid: 1892771
references.citation: Pathobiology. 2001;69(3):127-35
references.pmid: 11872958
references.citation: Gastroenterology. 2004 May;126(5):1330-6
references.pmid: 15131794
references.citation: Biochem Biophys Res Commun. 1994 Jan 14;198(1):318-27
references.pmid: 8292036
references.citation: Cancer Res. 2005 Dec 1;65(23):11193-202
references.pmid: 16322270
references.citation: Gastrointest Endosc. 2005 Sep;62(3):383-9
references.pmid: 16111956
references.citation: Glycoconj J. 1997 Aug;14(5):585-91
references.pmid: 9298691
references.citation: Pathol Res Pract. 2000;196(4):259-63
references.pmid: 10782470
references.citation: J Hepatol. 2000 Jun;32(6):946-54
references.pmid: 10898315
references.citation: J Gastroenterol Hepatol. 1999 May;14(5):436-45
references.pmid: 10355508
references.citation: Am J Epidemiol. 1998 Feb 15;147(4):407-13
references.pmid: 9508109
references.citation: Ann Surg. 2004 May;239(5):651-7; discussion 657-9
references.pmid: 15082969
references.citation: Cancer Res. 1997 Dec 1;57(23):5201-6
references.pmid: 9393734
references.citation: Clin Gastroenterol Hepatol. 2005 Oct;3(10):967-73
references.pmid: 16234041
references.citation: Clin Cancer Res. 2000 Aug;6(8):2969-72
references.pmid: 10955772
references.citation: J Proteome Res. 2009 Feb;8(2):483-92
references.pmid: 19072160
references.citation: Int J Cancer. 1996 Aug 22;69(4):290-4
references.pmid: 8797870
references.citation: Int J Cancer. 1993 Jul 30;54(6):972-7
references.pmid: 7687590
references.citation: Glycoconj J. 2007 Nov;24(8):411-20
references.pmid: 17457671
references.citation: Immunol Cell Biol. 2005 Aug;83(4):429-39
references.pmid: 16033539
references.citation: Am J Surg Pathol. 1999 Nov;23(11):1320-7
references.pmid: 10555000
references.citation: Mol Oncol. 2007 Sep;1(2):216-25
references.pmid: 19305640
references.citation: Ann Surg. 2006 May;243(5):673-80; discussion 680-3
references.pmid: 16633003