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Clinical Studies

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

British Journal of Cancer volume 126, pages 1387–1393 (2022)Cite this article

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Abstract

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.

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Fig. 1
Fig. 2: Receiver-operating characteristic curves for multivariable models.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

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.

Funding

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.

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Author notes

  1. Deceased: Hans Jørgen Nielsen.

Authors and Affiliations

  1. Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark

    Jakob Kleif, Linnea Ferm, Ib Jarle Christensen & Hans Jørgen Nielsen

  2. Department of Surgery, Hillerød Hospital, Hillerød, Denmark

    Jakob Kleif & Jesper Vilandt

  3. Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Jakob Kleif, Lars Nannestad Jørgensen & Hans Jørgen Nielsen

  4. Digestive Disease Center, Bispebjerg Hospital, Copenhagen, Denmark

    Lars Nannestad Jørgensen & Morten Rasmussen

  5. Gastro Unit, Section for Gastroenterology, Herlev Hospital, Herlev, Denmark

    Jakob W. Hendel

  6. Department of Surgery, Herning Hospital, Herning, Denmark

    Mogens R. Madsen

  7. Department of Surgery, Horsens Hospital, Horsens, Denmark

    Søren Brandsborg

  8. Department of Public Health Programmes and University Research Clinic for Cancer Screening, Randers Regional Hospital, Randers, Denmark

    Lars Maagaard Andersen & Berit Andersen

  9. Department of Surgery, Viborg Hospital, Viborg, Denmark

    Ali Khalid

  10. Department of Pathology, Herlev University Hospital, Herlev, Denmark

    Peter Ingeholm

  11. Abbott Laboratories, Abbott Diagnostics Division, Abbott Park, IL, USA

    Gerard J. Davis & Susan H. Gawel

  12. Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam UMC, AMC & VUMC, Amsterdam, The Netherlands

    Frans Martens

  13. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Berit Andersen

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Contributions

HJN conceived the study and provided the funding. LNJ, JWH, MRM, JV, LM, AK, BA, MR, SG, GJD and IJC helped design the study. LNJ, JWH, MRM, JV, SB, LM, AK, PI, LF, GJD, FM, BA and MR acquired the data. JK, IJC and HJN interpreted the results. JK wrote the draft. All authors revised the manuscript, approved the final version and agreed to be fully accountable for all aspects of the work.

Corresponding author

Correspondence to Jakob Kleif.

Ethics declarations

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki, and approved by the Ethics Committee at the Capital Region of Denmark (H-4-2013-050) and the Danish Data Protection Agency (2007-58-0015/HVH-2013-022). All participants signed an informed consent form.

Consent to publish

Not applicable.

Competing interests

SG and GJD are employees of Abbott Laboratories Inc. The remaining authors declare no competing interests.

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Kleif, J., Jørgensen, L.N., Hendel, J.W. et al. Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening. Br J Cancer 126, 1387–1393 (2022). https://doi.org/10.1038/s41416-022-01712-x

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