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

Int J Cancer. 2017 Mar 15;140(6):1436-1446. doi: 10.1002/ijc.30558.

Abstract

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.

Keywords: blood-based biomarkers; colorectal cancer; detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / diagnostic imaging
  • Adenoma / blood*
  • Adenoma / diagnosis
  • Adenoma / diagnostic imaging
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Colonic Diseases / blood
  • Colonoscopy
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / diagnostic imaging
  • Early Detection of Cancer*
  • Female
  • Humans
  • Male
  • Models, Biological
  • Neoplasm Proteins / blood*
  • Neoplasms / blood
  • Predictive Value of Tests
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins