*6.3.3 miRNA*

The role of circulating, exosome-free miRNAs as potential diagnostic and prognostic biomarkers in CRC has been extensively investigated over the past 5 years [111–116]. However, owing to extensive heterogeneity between several studies, it has been difficult to gauge their clinical worth in terms of sensitivity and specificity, which has often been described as 'modest'. Encouragingly, recent studies have suggested that by using miRNA panels or signatures, the predictive accuracy of these assays can be significantly enhanced [117, 118]. In mCRC, only a few studies have addressed the role of circulating miRNAs as predictive biomarkers to systemic therapy [119]. Conceptually, miRNA assays could be used in conjunction with ctDNA, or with the aforementioned biomarkers, to facilitate accurate read-outs for improved sensitivity and specificity.
