title: Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers.
abstract: Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Michael
authors.identifier: 0000-0002-8142-9030
authors.initials: M
authors.lastname: Wilhelmsen
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Rasmussen
authors.affiliation: Department of Surgical Gastroenterology, Bispebjerg Hospital, University of Copenhagen, København, Denmark.
authors.forename: Lars N
authors.initials: LN
authors.lastname: Jørgensen
authors.affiliation: Department of Surgical Gastroenterology, Herning Hospital, University of Copenhagen, Herning, Denmark.
authors.forename: Mogens R
authors.initials: MR
authors.lastname: Madsen
authors.affiliation: Department of Surgical Gastroenterology, Hillerød Hospital, University of Copenhagen, Hillerød, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Vilandt
authors.affiliation: Department of Clinical Biochemistry, Hillerød Hospital, Denmark.
authors.forename: Thore
authors.initials: T
authors.lastname: Hillig
authors.affiliation: Department of Surgical Gastroenterology, Horsens Hospital, University of Copenhagen, Horsens, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Klaerke
authors.affiliation: Department of Surgical Gastroenterology, Randers Hospital, University of Copenhagen, Randers, Denmark.
authors.forename: Knud T
authors.initials: KT
authors.lastname: Nielsen
authors.affiliation: Department of Surgical Gastroenterology, Aarhus Hospital, University of Copenhagen, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Laurberg
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: Cancer Core R&D, Abbott Diagnostics Division, Abbott Park, Chicago, IL, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Gawel
authors.affiliation: Cancer Core R&D, Abbott Diagnostics Division, Abbott Park, Chicago, IL, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Core R&D, Abbott Diagnostics Division, Abbott Park, Chicago, IL, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.affiliation: Department of Clinical Biochemistry, VU medical center, Amsterdam, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Heijboer
authors.affiliation: Department of Clinical Biochemistry, VU medical center, Amsterdam, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Martens
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging; D000236:Adenoma / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D003108:Colonic Diseases / Q000097:blood; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000097:blood*; D009369:Neoplasms / Q000097:blood; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: blood-based biomarkers; colorectal cancer; detection