Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Kleif, Jakob
  • Jørgensen, Lars Nannestad
  • Jakob W. Hendel
  • Mogens R. Madsen
  • Jesper Vilandt
  • Søren Brandsborg
  • Lars Maagaard Andersen
  • Ali Khalid
  • Peter Ingeholm
  • Linnea Ferm
  • Gerard J. Davis
  • Susan H. Gawel
  • Frans Martens
  • Berit Andersen
  • Morten Rasmussen
  • Ib Jarle Christensen
  • Hans Jørgen Nielsen

Background: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population. Methods: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy. Results: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66–0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin. Conclusion: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

OriginalsprogEngelsk
TidsskriftBritish Journal of Cancer
Vol/bind126
Udgave nummer10
Sider (fra-til)1387-1393
Antal sider7
ISSN0007-0920
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
This study was financially supported by: The Andersen-Isted Fund, The Augustinus Foundation, The Vilhelm Bang Fund, The Beckett Fund, The Inger Bonnén Fund, The Hans and Nora Buchard Fund, CEO Jens Bærentsen, The Walter and O. Kristiane Christensen Fund, The Poul Martin Christiansen Fund, The Aase and Ejnar Danielsen Fund, The Danish Cancer Society, The Erichsen Family Fund, The Knud and Edith Eriksen Fund, The Svend Espersen Fund, The Elna and Jørgen Fagerholt Fund, The Sofus Friis Fund, The Torben and Alice Frimodt Fund, The Eva and Henry Frænkel Fund, The Gangsted Fund, The Thora and Viggo Grove Fund, The Erna Hamilton Fund, The Sven and Ina Hansen Fund, The Hede-Nielsen Family Fund, The Søren and Helene Hempel Fund, The Henrik Henriksen Fund, The Carl and Ellen Hertz Fund, The Elisa and Jørgen Holm Fund, The Humanitarian Foundation, The Ovita Juhl Fund, Foundation Jochum, The KID Fund, The Kornerup Fund, The Linex Fund, The Aage and Johanne Louis-Hansen Fund, The Mid Jutland Newspaper Fund, The Dagmar Marshall Fund, The Muusfeldt Fund, The Børge Nielsen Fund, The Inge and Jørgen Nielsen Fund, The Michael H. Nielsen Fund, The Arvid Nilsson Fund, The Obel Family Fund, The Orient Fund, The Krista and Viggo Petersen Fund, The Willy and Ingeborg Reinhard Fund, The Katrine and Vigo Skovgaard Fund, The Toyota Fund, The Tryg Fund, The Vissing Fund, The Else og Mogens Wedell-Wedellsborg Fund.

Funding Information:
The commitment and excellent work of the research nurses and secretaries at the participating Danish hospitals at the Central Denmark Region and the Capital Region of Denmark are highly appreciated. In addition, the secretaries at the screening centres at Randers and Bornholm Hospitals are thanked for their diligent identification of subjects with FIT-positive and -negative screening results, respectively.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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