Detection of colorectal neoplasia: Combination of eight blood‐based, cancer‐associated protein biomarkers

• Published in: International journal of cancer Vol. 140; no. 6; pp. 1436 - 1446
• Main Authors: Wilhelmsen, Michael, Christensen, Ib J., Rasmussen, Louise, Jørgensen, Lars N., Madsen, Mogens R., Vilandt, Jesper, Hillig, Thore, Klærke, Michael, Nielsen, Knud T., Laurberg, Søren, Brünner, Nils, Gawel, Susan, Yang, Xiaoqing, Davis, Gerard, Heijboer, Annemieke, Martens, Frans, Nielsen, Hans J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15-03-2017
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - diagnosis; Adenocarcinoma - diagnostic imaging; Adenoma - blood; Adenoma - diagnosis; Adenoma - diagnostic imaging; Area Under Curve; Biomarkers; Biomarkers, Tumor - blood; blood‐based biomarkers; Cancer; Colonic Diseases - blood; Colonoscopy; Colorectal cancer; Colorectal Neoplasms - blood; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - diagnostic imaging; detection; Early Detection of Cancer; Female; Histology; Humans; Male; Medical research; Models, Biological; Neoplasm Proteins - blood; Neoplasms - blood; Predictive Value of Tests; Proteins; Sensitivity and Specificity; blood-based biomarkers; detection; colorectal cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30558

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer‐associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19‐9, CEA, hs‐CRP, CyFra21‐1, Ferritin, Galectin‐3 and TIMP‐1 were determined in EDTA‐plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high‐risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010–2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high‐risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had ‘clean’ colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood‐based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs‐CRP, CyFra21‐1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.
What's new?
How can colorectal cancer be detected earlier? ‘Colonoscopies for everyone’ might be effective, but it is far too expensive. Instead, these authors propose a set of eight protein biomarkers that could signal the presence of cancer. They tested the blood‐based biomarker screening in patients who were already seeking a colonoscopy after experiencing bowel‐related symptoms. Of the nearly 4,700 subjects tested, colonoscopy uncovered 512 colorectal cancers and 399 high‐risk adenomas. The panel of biomarkers, in combination, successfully predicted the cancers. Next, the markers will need to be tested on asymptomatic subjects, to determine their usefulness as a general screening tool.