Risk-Predictive and Diagnostic Biomarkers for Colorectal Cancer; a Systematic Review of Studies Using Pre-Diagnostic Blood Samples Collected in Prospective Cohorts and Screening Settings

Abstract

This systematic review summarizes the evidence for blood-based colorectal cancer biomarkers from studies conducted in pre-diagnostic, asymptomatic settings. Of 1372 studies initially identified, the final selection included 30 studies from prospective cohorts and 23 studies from general screening settings. Overall, the investigations had high quality but considerable variability in data analysis and presentation of results, and few biomarkers demonstrated a clinically relevant discriminatory ability. One of the most promising biomarkers was the anti-p53 antibody, with consistent findings in one screening cohort and in the 3–4 years prior to diagnosis in two prospective cohort studies. Proteins were the most common type of biomarker assessed, particularly carcinoembryonic antigen (CEA) and C-reactive protein (CRP), with modest results. Other potentially promising biomarkers included proteins, such as AREG, MIC-1/GDF15, LRG1 and FGF-21, metabolites and/or metabolite profiles, non-coding RNAs and DNA methylation, as well as re-purposed routine lab tests, such as ferritin and the triglyceride–glucose index. Biomarker panels generally achieved higher discriminatory performance than single markers. In conclusion, this systematic review highlighted anti-p53 antibodies as a promising blood-based biomarker for use in colorectal cancer screening panels, together with other specific proteins. It also underscores the need for validation of promising biomarkers in independent pre-diagnostic settings.