TY - JOUR

T1 - Early detection of colorectal neoplasia

T2 - application of a blood-based serological protein test on subjects undergoing population-based screening

AU - Kleif, Jakob

AU - Jørgensen, Lars Nannestad

AU - Hendel, Jakob W.

AU - Madsen, Mogens R.

AU - Vilandt, Jesper

AU - Brandsborg, Søren

AU - Andersen, Lars Maagaard

AU - Khalid, Ali

AU - Ingeholm, Peter

AU - Ferm, Linnea

AU - Davis, Gerard J.

AU - Gawel, Susan H.

AU - Martens, Frans

AU - Andersen, Berit

AU - Rasmussen, Morten

AU - Christensen, Ib Jarle

AU - Nielsen, Hans Jørgen

N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1038/s41416-022-01712-x

DO - 10.1038/s41416-022-01712-x

M3 - Journal article

C2 - 35091694

AN - SCOPUS:85123868950

VL - 126

SP - 1387

EP - 1393

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

SN - 0007-0920

IS - 10

ER -