title: Collagen peptides in urine: a new promising biomarker for the detection of colorectal liver metastases.
abstract: BACKGROUND
  For both patients and the outpatient clinic the frequent follow-up visits after a resection of colorectal cancer (CRC) are time consuming and due to large patient numbers expensive. Therefore it is important to develop an effective non-invasive test for the detection of colorectal liver metastasis (CRLM) which could be used outside the hospital. The urine proteome is known to provide detailed information for monitoring changes in the physiology of humans. Urine collection is non-invasive and urine naturally occurring peptides (NOPs) have the advantage of being easily accessible without labour-intensive sample preparation. These advantages make it potentially useful for a quick and reliable application in clinical settings. In this study, we will focus on the identification and validation of urine NOPs to discriminate patients with CRLM from healthy controls.
  
  
  METHODS
  Urine samples were collected from 24 patients with CRLM and 25 healthy controls. In the first part of the study, samples were measured with a nano liquid chromatography (LC) system (Thermo Fisher Scientific, Germaring, Germany) coupled on-line to a hybrid linear ion trap/Orbitrap mass spectrometer (LTQ-Orbitrap-XL, Thermo Fisher Scientific, Bremen, Germany). A discovery set was used to construct the model and consecutively the validation set, being independent from the discovery set, to check the acquired model. From the peptides which were selected, multiple reaction monitoring (MRM's) were developed on a UPLC-MS/MS system.
  
  
  RESULTS
  Seven peptides were selected and applied in a discriminant analysis a sensitivity of 84.6% and a specificity of 92.3% were established (Canonical correlation:0.797, Eigenvalue:1.744, F:4.49, p:0.005). The peptides AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGA P(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG were selected for further quantitative analysis which showed a sensitivity of 88% and a specificity of 88%.
  
  
  CONCLUSIONS
  Urine proteomic analysis revealed two very promising peptides, both part from collagen type 1, AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG which could detect CRLM in a non-invasive manner.
authors: Department of Surgery, Division of Transplantation and Hepatobiliary Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Mirelle E E
authors: ME
authors: Bröker
authors: Zarina S
authors: ZS
authors: Lalmahomed
authors: Henk P
authors: HP
authors: Roest
authors: Nick A
authors: NA
authors: van Huizen
authors: Lennard J M
authors: LJ
authors: Dekker
authors: Wim
authors: W
authors: Calame
authors: Cornelis
authors: C
authors: Verhoef
authors: Jan N M
authors: JN
authors: Ijzermans
authors: Theo M
authors: TM
authors: Luider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000652:urine*; D002277:Carcinoma / Q000175:diagnosis* / Q000556:secondary / Q000652:urine; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003094:Collagen / Q000652:urine*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary / Q000652:urine; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000652:urine*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides; D003094:Collagen
references: Lab Invest. 1984 Jul;51(1):57-74
references: 6376944
references: J Pathol. 2003 Jul;200(4):423-8
references: 12845610
references: Lancet. 1994 Jun 4;343(8910):1405-10
references: 7515134
references: Semin Oncol. 2003 Jun;30(3):349-60
references: 12870136
references: Anticancer Res. 2012 Dec;32(12):5183-91
references: 23225415
references: Annu Rev Cell Dev Biol. 2009;25:567-95
references: 19575644
references: Mol Cell Proteomics. 2007 Jul;6(7):1147-57
references: 17360931
references: Proteomics Clin Appl. 2011 Jun;5(5-6):211-3
references: 21618704
references: Trends Biochem Sci. 2011 Jan;36(1):7-18
references: 20728359
references: Ann N Y Acad Sci. 2006 Nov;1089:228-36
references: 17261770
references: J Hepatol. 1990 Jul;11(1):43-52
references: 1697872
references: Proteomics Clin Appl. 2007 Jul 10;1(8):792
references: 20107618
references: Mol Cell Proteomics. 2009 Oct;8(10):2296-307
references: 19564150
references: Gut. 2013 Jan;62(1):122-30
references: 22580416
references: Nat Rev Cancer. 2003 Apr;3(4):267-75
references: 12671665
references: Lab Invest. 1991 Feb;64(2):157-66
references: 1997730
references: Curr Top Dev Biol. 2006;72:205-36
references: 16564336
references: Dis Colon Rectum. 2008 Nov;51(11):1675-80
references: 18633674
references: Mol Cell Proteomics. 2005 Dec;4(12):2010-21
references: 16249172
references: Proteomics Clin Appl. 2010 Apr;4(4):464-78
references: 21137064