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.

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

“…2 Recent literatures showed that exosomes are closely related to tumor development and metastasis and even influence the therapeutic effect in cancer patients. 6,7 The stable presence of miRNAs in body fluids is partly because they are packed into microvesicles or exosomes. 8 Besides, miRNAs and mRNAs in exosomes are functional.…”

Liquid biopsy - emergence of a new era in personalized cancer care

“…Thus, mutation can be missed in cases of contamination, widespread necrosis, or when only small quantities of DNA are available [153]. Perhaps for the same reason, there is a lack of consistent and robust results of circulating genomic materials, with many apparently contradictory reports in the literature [154]. Lee and group [107] found one of their patients had all COSMIC mutations though the patient was negative for EpCAM-positive CTCs.…”

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

“…Perfect complementarity between miRNA and mRNA leads to cleavage and degradation of the latter, whereas imperfect complementarity results into suppression of the translation of the target mRNA (Tang 2005). Otherwise, mature miRNAs can be secreted by cells in biological fluids including plasma, serum, saliva and several other body fluids (Larrea et al 2016). miRNAs can be released by passive secretion from cells that lost their integrity after tissue injury, cell apoptosis or necrosis (Laterza et al 2009).…”

“…An alternative hypothesis is that miRNAs are actively secreted from cells in microvesicles such as exosomes or shedding vesicles (Valadi et al 2007) (Mohammadian et al 2013). NGS is used to detect both novel and known miRNAs, with the limit that this technique is relatively expensive (Larrea et al 2016). Finally, ISH technology may provide information regarding the exact localization of miRNAs within the tumor cell itself or within tumor stromal cells (Nuovo 2010), but has limited relevance as to circulating miRNAs are concerned.…”