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

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed 8 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: 1: CRC and high risk adenoma and 2: CRC. Logistic regression was performed. Final reduced models were constructed selecting the 4 biomarkers with the highest likelihood scores. Subjects (N=4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer (CC) and 193 rectal cancer (RC). Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1342 had non-neoplastic bowell disease, and 1978 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 selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUC's were 0.76 and, 0.84, respectively. The postive predictive value (PPV) at 90% sensitivity was 25% for endpoint 1 and the negative predictive value (NPV) was 93%. For endpoint 2 the PPV was 18% and the NPV was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high-risk of presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC. This article is protected by copyright. All rights reserved.