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Review
. 2021 Aug 31;13(17):4406.
doi: 10.3390/cancers13174406.

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

Sophia Harlid  1 , Marc J Gunter  2 , Bethany Van Guelpen  1   3
Affiliations
Review

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

Sophia Harlid et al. Cancers (Basel). .

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.

Keywords: biomarkers; cancer screening tests; colorectal neoplasms; early detection of cancer; liquid biopsy; precision medicine.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Figures

Figure 1
Figure 1
Flow diagram illustrating the selection of studies assessing blood-based risk-predictive and diagnostic biomarkers of colorectal cancer using pre-diagnostic samples from asymptomatic individuals, i.e., samples collected in prospective cohorts or general screening settings. During data extraction, an additional five studies were excluded due to lack of key information (n = 1), too small sample size (n = 2) or non-general screening population (n = 2). * Other sources included reference lists, review articles, the article collections of the authors and post hoc searches of PubMed.
Figure 2
Figure 2
Potential applications of pre-diagnostic biomarkers for prevention and early detection of colorectal cancer.
See this image and copyright information in PMC

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