title: Plasma TIMP-1 and CEA as Markers for Detection of Primary Colorectal Cancer: A Prospective Validation Study Including Symptomatic and Non-symptomatic Individuals.
abstract: OBJECTIVE
  The combination of plasma tissue inhibitor of metalloproteinases-1 (1) and CEA has been shown to have utility in early detection of colorectal cancer (2). A prospective study was performed to validate previous findings.
  
  
  METHODS
  Individuals undergoing large bowel endoscopy were prospectively included (N=1965). Baseline data and co-morbidity were recorded. The primary end-point was the detection of CRC. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined using an automated analysis platform when all samples were collected.
  
  
  RESULTS
  CRC was detected in 32 individuals, 24 with colonic cancer (CC) and 8 with rectal cancer (RC). Other findings were 265 with adenomas and 889 with non-neoplastic pathology. The biomarker levels were elevated in plasma from patients with CRC, but also from patients with various co-morbidities compared to individuals without any findings at endoscopy. Univariate analysis demonstrated that both markers were significant predictors of CRC. The odds ratios (OR) for an elevated TIMP-1 level for the detection of CRC was 6.2 [95% confidence interval (CI)=3.1-13.0, p<0.0001] and for an elevated CEA level was 2.4 (95% CI=1.9-2.9, p<0.0001). A subset analysis with CC as the end-point showed an OR for TIMP-1 of 7.0 (95% CI=3.2-15.3, p<0.0001). Multivariable analysis including TIMP-1, CEA and age resulted in an OR for TIMP-1 of 2.0 (95% CI=0.7-5.2, p=0.078) and for CEA the OR was 2.2 (95% CI=1.8-2.8, p<0.0001).
  
  
  CONCLUSIONS
  This prospective study validates a previous study testing the detection of CRC based on TIMP-1 and CEA levels (3).
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark ib.jarle.christensen@regionh.dk.
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Section of Molecular Disease Biology, Faculty of Health Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: Abbott Cancer Diagnostic Research, Chicago, IL, U.S.A.
authors.forename: Barry
authors.initials: B
authors.lastname: Dowell
authors.affiliation: Abbott Cancer Diagnostic Research, Chicago, IL, U.S.A.
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark Faculty of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Nielsen
authors.affiliation: Sydney Colorectal Associates, Prince of Wales Hospital, Randswick, NSW, Australia.
authors.forename: Graham
authors.initials: G
authors.lastname: Newstead
authors.affiliation: Sydney Colorectal Associates, St. George Hospital, Kogarah, NSW, Australia.
authors.forename: Denis
authors.initials: D
authors.lastname: King
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000201:enzymology*; D004724:Endoscopy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: Colorectal cancer; biomarkers; bowel endoscopy; early detection; screening