Discovery and validation of new potential biomarkers for early detection of colon cancer

PLoS One. 2014 Sep 12;9(9):e106748. doi: 10.1371/journal.pone.0106748. eCollection 2014.

Abstract

Background: Accurate detection of characteristic proteins secreted by colon cancer tumor cells in biological fluids could serve as a biomarker for the disease. The aim of the present study was to identify and validate new serum biomarkers and demonstrate their potential usefulness for early diagnosis of colon cancer.

Methods: The study was organized in three sequential phases: 1) biomarker discovery, 2) technical and biological validation, and 3) proof of concept to test the potential clinical use of selected biomarkers. A prioritized subset of the differentially-expressed genes between tissue types (50 colon mucosa from cancer-free individuals and 100 normal-tumor pairs from colon cancer patients) was validated and further tested in a series of serum samples from 80 colon cancer cases, 23 patients with adenoma and 77 cancer-free controls.

Results: In the discovery phase, 505 unique candidate biomarkers were identified, with highly significant results and high capacity to discriminate between the different tissue types. After a subsequent prioritization, all tested genes (N = 23) were successfully validated in tissue, and one of them, COL10A1, showed relevant differences in serum protein levels between controls, patients with adenoma (p = 0.0083) and colon cancer cases (p = 3.2e-6).

Conclusion: We present a sequential process for the identification and further validation of biomarkers for early detection of colon cancer that identifies COL10A1 protein levels in serum as a potential diagnostic candidate to detect both adenoma lesions and tumor.

Impact: The use of a cheap serum test for colon cancer screening should improve its participation rates and contribute to decrease the burden of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / blood
  • Adenoma / diagnosis
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Collagen Type X / metabolism
  • Colonic Neoplasms / blood*
  • Colonic Neoplasms / diagnosis*
  • Early Detection of Cancer*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • Collagen Type X
  • Neoplasm Proteins

Grant support

This work was supported by the Catalan Institute of Oncology (ICO) and the Private Foundation of the Biomedical Research Institute of Bellvitge (IDIBELL), the Instituto de Salud Carlos III [grants PI08-1635, PI08-1359, PS09-1037, PI11-1439], CIBERESP CB06/02/2005 and the “Acción Transversal del Cancer”, the Catalan Government DURSI [grant 2009SGR1489], the Fundació Privada Olga Torres (FOT), the Spanish Association Against Cancer (AECC) Scientific Foundation, the European Commission [grant FP7-COOP-Health-2007-B HiPerDART], and Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncología de Catalunya (XBTC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.