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Bispebjerg Hospital - a part of Copenhagen University Hospital

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers

Research output: Contribution to journalJournal articlepeer-review


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  • Michael Wilhelmsen
  • Ib J Christensen
  • Louise Rasmussen
  • Lars N Jørgensen
  • Mogens R Madsen
  • Jesper Vilandt
  • Thore Hillig
  • Michael Klaerke
  • Knud T Nielsen
  • Søren Laurberg
  • Nils Brünner
  • Susan Gawel
  • Xiaoqing Yang
  • Gerard Davis
  • Anne Meike Heijboer
  • Frans Martens
  • Hans J Nielsen
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Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed 8 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: 1: CRC and high risk adenoma and 2: CRC. Logistic regression was performed. Final reduced models were constructed selecting the 4 biomarkers with the highest likelihood scores. Subjects (N=4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer (CC) and 193 rectal cancer (RC). Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1342 had non-neoplastic bowell disease, and 1978 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 selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUC's were 0.76 and, 0.84, respectively. The postive predictive value (PPV) at 90% sensitivity was 25% for endpoint 1 and the negative predictive value (NPV) was 93%. For endpoint 2 the PPV was 18% and the NPV was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high-risk of presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalInternational Journal of Cancer
Issue number6
Pages (from-to)1436-1446
Publication statusPublished - 2017

ID: 49455582