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 - © 2022. The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/6
Y1 - 2022/6
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.
UR - http://www.scopus.com/inward/record.url?scp=85123868950&partnerID=8YFLogxK
U2 - 10.1038/s41416-022-01712-x
DO - 10.1038/s41416-022-01712-x
M3 - Journal article
C2 - 35091694
SN - 0007-0920
VL - 126
SP - 1387
EP - 1393
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 10
ER -