Discovery and Validation of New Potential Biomarkers for Early Detection of Colon Cancer

TLDR

Proteins secreted by colon cancer cells in biological fluids can serve as disease biomarkers. The study aims to identify and validate serum biomarkers for early colon cancer diagnosis. A three‑phase approach—discovery, technical and biological validation, and proof of concept—tested 23 prioritized genes in tissue and serum from 80 cancer cases, 23 adenoma patients, and 77 controls. Discovery yielded 505 candidate biomarkers; 23 were validated, with COL10A1 showing significant serum level differences between controls, adenoma, and cancer patients.

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.