New Concepts in Cancer Biomarkers: Circulating miRNAs in Liquid Biopsies

Abstract

The effective and efficient management of cancer patients relies upon early diagnosis and/or the monitoring of treatment, something that is often difficult to achieve using standard tissue biopsy techniques. Biological fluids such as blood hold great possibilities as a source of non-invasive cancer biomarkers that can act as surrogate markers to biopsy-based sampling. The non-invasive nature of these "liquid biopsies" ultimately means that cancer detection may be earlier and that the ability to monitor disease progression and/or treatment response represents a paradigm shift in the treatment of cancer patients. Below, we review one of the most promising classes of circulating cancer biomarkers: microRNAs (miRNAs). In particular, we will consider their history, the controversy surrounding their origin and biology, and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.

Keywords: cfmiRNAs; liquid biopsies; miRNAs.

Figure 1

Chronological timeline of key discoveries in the microRNA (miRNA) field and their relevance to cancer. The overlapping plot depicts the number of PubMed-indexed publications for miRNA (dark blue) or miRNA related to cancer (light blue).

Figure 2

Selected circulating cell-free microRNAs (cfmiRNAs) and their functional role in the hallmarks of cancer.The figure lists some examples of biomarker cfmiRNAs (with a focus on the ones described in this review) that regulate genes involved in the different hallmarks of cancer as defined by Hanahan and Weinberg [18].

Figure 3

Origin of extracellular RNA. Several hypotheses have been proposed to explain the presence of miRNA in biological fluids, including the passive release of miRNA from broken cells and tissues and the active secretion from cells in microvesicles or conjugated to RNA-binding proteins. Cell-free miRNA can be detected in different body fluids including plasma, serum, saliva, tears, urine, amniotic fluid, colostrum, breast milk, bronchial lavage, cerebrospinal fluid, peritoneal fluid, pleural fluid, and seminal fluid and also in feces. Ago 1–4: Argonaute proteins 1–4; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; MVB: Multivesicular body.

Figure 4

Comparison of methods commonly used to study extracellular RNA. Color code indicates the relative feasibility of that particular technique based on a given feature, from light blue (more feasible), through turquoise, to dark blue (less feasible). Data analysis: Easy (feasible in any molecular biology lab), Moderate (various software platforms available), Difficult (requires advanced computational infrastructure).