Novel biomarkers for patient stratification in colorectal cancer: A review of definitions, emerging concepts, and data

Table 1 Biomarker types and definitions

Biomarker type	Objective
Diagnostic biomarker	These aim to identify the type of cancer, e.g., PSA, CEA. They may also be used to monitor or detect disease recurrence
Pharmacological biomarker	These are used to measure response to a specific drug treatment. They are based on accurate pharmokinetic data and measure treatment response in early drug trials, e.g., drug therapy to angiogenesis
Predictive biomarker	These are used to identify individuals who will most likely show a survival benefit to a specific targeted treatment, e.g., improvement in local recurrence risk following treatment for circumferential resection margin involvement
Prognostic biomarker	These indicate the progress of disease and to estimate the risk of disease recurrence for example. They are used to estimate survival outcome and are independent of treatment strategy, e.g., nodal disease
Risk/predisposition biomarker	These aim to identify individuals who are at significant risk of developing tumours, e.g., MLH1 gene
Screening biomarker	These are used to identify disease at an early stage, e.g., PSA
Surrogate response biomarker	These can be used as an alternative to a clinically meaningful endpoint. Therefore there must be correlation with a clinical endpoint, e.g., CEA

Table 2 Candidate liquid biopsy/circulating miRNA biomarkers[145]

Expression level	Diagnostic biomarker	Prognostic biomarker (malignant potential, tumor recurrence)	Predictive biomarker (chemosensitivity)
High	miR-92a, miR-141, let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, miR-23a, miR-378	miR-141, miR-320, miR-596, miR-203	miR-106a, miR-484, miR-130b
Low		miR-15a, miR-103, miR-148a, miR451

Adapted from Tsutomu Kawaguchi et al. Circulating MicroRNAs: A Next-Generation Clinical Biomarker for Digestive System Cancers. Int J Mol Sci 2016; 17: 1459.