title: Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides.
abstract: BACKGROUND
  Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30% of inflammatory bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the overlap of clinical and histologic features. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) permits a histology-directed cellular protein analysis of tissues. As a pilot study, we evaluated the ability of histology-directed MALDI-MS to determine the proteomic patterns for potential differences between CC and UC specimens.
  
  
  METHODS
  Mucosal and submucosal layers of CC and UC colon resection samples were analyzed after histologic assessment. To determine whether MALDI-MS would distinguish inflammation, the uninflamed (n = 21) versus inflamed submucosa (n = 22) were compared in UC and the uninflamed (n = 17) versus inflamed submucosa (n = 20) in CC. To determine whether there were proteomic differences between the colitides, the uninflamed UC submucosa (n = 21) was compared versus the uninflamed CC submucosa (n = 17), the inflamed UC submucosa (n = 22) was compared versus the inflamed CC submucosa (n = 20), and inflamed UC mucosa versus inflamed CC mucosa. Pairwise statistics comparisons of the subsets were performed.
  
  
  RESULTS
  Pairwise comparative analyses of the clinical groups allowed identifying subsets of features important for classification. Comparison of inflamed versus uninflamed CC submucosa showed two significant peaks: m/z 6445 (P = 0.0003) and 12692 (P = 0.003). In the case of inflamed versus uninflamed UC submucosa, several significant differentiating peaks were found, but classification was worse. Comparisons of the proteomic spectra of inflamed submucosa between UC and CC identified two discrete significant peaks: m/z 8773 (P = 0.006) and 9245 (P = 0.0009). Comparisons of the proteomic spectra of uninflamed submucosa between UC and CC identified three discrete significant peaks: m/z 2778 (P = 0.005), 9232 (P = 0.005), and 9519 (P = 0.005). No significantly different features were found between UC and CC inflamed mucosa.
  
  
  CONCLUSIONS
  MALDI-MS was able to distinguish CC and UC specimens while profiling the colonic submucosa. Further analyses and protein identification of the differential protein peaks may aid in accurately diagnosing IBD and developing appropriate personalized therapies.
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, Tennessee 37208-3599, USA. amkoma@mmc.edu
authors.forename: Amosy E
authors.initials: AE
authors.lastname: M'Koma
authors.forename: Erin H
authors.initials: EH
authors.lastname: Seeley
authors.forename: Mary K
authors.initials: MK
authors.lastname: Washington
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.forename: Roberta L
authors.initials: RL
authors.lastname: Muldoon
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Herline
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wise
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D016002:Discriminant Analysis; D006801:Humans; D009092:Mucous Membrane / Q000378:metabolism*; D010449:Peptide Mapping; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D020543:Proteome
references.citation: Clin Cancer Res. 2010 Jan 15;16(2):681-90
references.pmid: 20068102
references.citation: J Mol Diagn. 2006 Feb;8(1):51-61
references.pmid: 16436634
references.citation: J Clin Pathol. 2002 Dec;55(12):955-60
references.pmid: 12461067
references.citation: Biochem Pharmacol. 2007 May 1;73(9):1422-33
references.pmid: 17258689
references.citation: J Clin Pathol. 2006 Oct;59(10):1066-72
references.pmid: 16565224
references.citation: Anal Chem. 2004 Mar 1;76(5):87A-93A
references.pmid: 15008156
references.citation: Anal Chem. 2004 Feb 15;76(4):1145-55
references.pmid: 14961749
references.citation: Acta Chir Iugosl. 2000;47(4 Suppl 1):27-31
references.pmid: 11432239
references.citation: Am J Gastroenterol. 2005 Feb;100(2):414-23
references.pmid: 15667502
references.citation: Gut. 1987 Mar;28(3):336-8
references.pmid: 3570037
references.citation: Am J Gastroenterol. 2008 Jan;103(1):162-9
references.pmid: 17916108
references.citation: Gastrointest Endosc. 1987 Feb;33(1):15-7
references.pmid: 3557027
references.citation: Immunity. 2002 Nov;17(5):629-38
references.pmid: 12433369
references.citation: Inflamm Bowel Dis. 2008 Jul;14(7):942-8
references.pmid: 18300279
references.citation: Monogr Pathol. 1977;(18):50-94
references.pmid: 611415
references.citation: J Proteome Res. 2007 Mar;6(3):1114-25
references.pmid: 17330946
references.citation: Curr Gastroenterol Rep. 2003 Dec;5(6):487-92
references.pmid: 14602058
references.citation: Lancet. 2003 Aug 9;362(9382):433-9
references.pmid: 12927430
references.citation: J Postgrad Med. 2009 Apr-Jun;55(2):131-4
references.pmid: 19550060
references.citation: Clin Chem. 2006 Feb;52(2):171-81
references.pmid: 16339302
references.citation: Gastroenterol Clin North Am. 2002 Mar;31(1):21-39
references.pmid: 12122733
references.citation: Inflamm Bowel Dis. 2009 Feb;15(2):284-94
references.pmid: 18816633
references.citation: Ann Stat. 2009 Jan 1;37(5A):2178-2201
references.pmid: 19784398
references.citation: Clin Biochem. 2008 Aug;41(12):960-7
references.pmid: 18489908
references.citation: Gastroenterology. 1980 Jul;79(1):19-25
references.pmid: 7380218
references.citation: Mol Cell Proteomics. 2006 Oct;5(10):1975-83
references.pmid: 16849436
references.citation: Int J Colorectal Dis. 2007 Jun;22(6):581-9
references.pmid: 17109102
references.citation: AJR Am J Roentgenol. 2005 Jun;184(6):1843-7
references.pmid: 15908540
references.citation: N Engl J Med. 2002 Aug 8;347(6):417-29
references.pmid: 12167685
references.citation: BMC Med Genomics. 2010 May 04;3:14
references.pmid: 20441585
references.citation: World J Gastroenterol. 2009 Sep 14;15(34):4234-9
references.pmid: 19750566
references.citation: Pathol Res Pract. 2004;200(2):129-33
references.pmid: 15237921
references.citation: Gut. 1973 Apr;14(4):255-62
references.pmid: 4706906
references.citation: Gut. 2005 Mar;54(3):364-8
references.pmid: 15710984
references.citation: Inflamm Bowel Dis. 2003 Sep;9(5):290-301
references.pmid: 14555912