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

• Published in: British journal of cancer Vol. 126; no. 10; pp. 1387 - 1393
• Main Authors: Kleif, Jakob, Jørgensen, Lars Nannestad, Hendel, Jakob W., Madsen, Mogens R., Vilandt, Jesper, Brandsborg, Søren, Andersen, Lars Maagaard, Khalid, Ali, Ingeholm, Peter, Ferm, Linnea, Davis, Gerard J., Gawel, Susan H., Martens, Frans, Andersen, Berit, Rasmussen, Morten, Christensen, Ib Jarle, Nielsen, Hans Jørgen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2022; Nature Publishing Group
• Subjects: 692/4028/67/1504/1885; 692/4028/67/2322; 692/53/2421; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; C-Reactive Protein; Cancer; Cancer Research; Cancer screening; Colonoscopy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - epidemiology; Drug Resistance; Early Detection of Cancer - methods; Epidemiology; Feces; Ferritin; Ferritins; Galectin-3; Humans; Keratin-19; Mass Screening; Medical screening; Molecular Medicine; Occult Blood; Oncology; Serology; Tissue inhibitor of metalloproteinase 1
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-022-01712-x

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.