title: Proximal fluid proteome profiling of mouse colon tumors reveals biomarkers for early diagnosis of human colorectal cancer.
abstract: OBJECTIVE
  Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC.
  
  
  METHODS
  Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. The FabplCre;Apc(15lox/+) mouse model represents early-stage development of human sporadic CRC. Proximal fluids were collected from normal colon and colon tumors and subjected to in-depth proteome profiling by tandem mass spectrometry. Carcinoembryonic antigen (CEA) and CHI3L1 human serum protein levels were determined by ELISA.
  
  
  RESULTS
  Of the 2,172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (P < 0.05) and abundantly (>5-fold) more excreted by tumors than by controls. Further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including S100A9, MCM4, and four other proteins that have been proposed as candidate biomarkers for human CRC screening or surveillance, supporting the validity of our approach. For CHI3L1, we verified that protein levels were significantly increased in sera from patients with adenomas and advanced adenomas compared with control individuals, in contrast to the CRC biomarker CEA.
  
  
  CONCLUSIONS
  These data show that proximal fluid proteome profiling with a mouse tumor model is a powerful approach to identify candidate biomarkers for early diagnosis of human cancer, exemplified by increased CHI3L1 protein levels in sera from patients with CRC precursor lesions.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. rja.fijneman@vumc.nl
authors.forename: Remond J A
authors.initials: RJ
authors.lastname: Fijneman
authors.forename: Meike
authors.initials: M
authors.lastname: de Wit
authors.forename: Maral
authors.initials: M
authors.lastname: Pourghiasian
authors.forename: Sander R
authors.initials: SR
authors.lastname: Piersma
authors.forename: Thang V
authors.initials: TV
authors.lastname: Pham
authors.forename: Marc O
authors.initials: MO
authors.lastname: Warmoes
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Lavaei
authors.forename: Chloe
authors.initials: C
authors.lastname: Piso
authors.forename: Fiona
authors.initials: F
authors.lastname: Smit
authors.forename: Pien M
authors.initials: PM
authors.lastname: Delis-van Diemen
authors.forename: Sietze T
authors.initials: ST
authors.lastname: van Turenhout
authors.forename: Jochim S
authors.initials: JS
authors.lastname: Terhaar sive Droste
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Els C
authors.initials: EC
authors.lastname: Robanus-Maandag
authors.forename: Ron
authors.initials: R
authors.lastname: Smits
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Victor W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Connie R
authors.initials: CR
authors.lastname: Jimenez
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D002853:Chromatography, Liquid; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D012007:Rectum / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D002272:Carcinoembryonic Antigen; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D020543:Proteome