A group of three miRNAs can act as candidate circulating biomarkers in liquid biopsies from melanoma patients

Abstract

Background: Staging of melanoma and follow up after melanoma diagnosis aims at predicting risk and detecting progression or recurrence at early stage, respectively in order to timely start and/or change treatment. Tumor thickness according to Breslow, status of the sentinel node and value of the lactate dehydrogenase (LDH) are well-established prognostic markers for metastatic risk, but reliable biomarkers identifying early recurrence or candidates who may benefit best from medical treatment are still warranted. Liquid biopsy has emerged to be a suitable method for identifying biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows analyzing circulating analytes, including extracellular vesicles.

Methods: In this study we have explored the use of 7 miRNAs, namely hsa-miR-149-3p, hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-200c-3p, hsa-miR-134-5p, hsa-miR-144-3p and hsa-miR-221-3p in plasma exosomes to discriminate melanoma patients from controls without melanoma in a cohort of 92 individuals.

Results and discussion: Our results showed that three out seven miRNAs, namely hsa-miR-200c-3p, hsa-miR-144-3p and hsa-miR-221-3p were differentially expressed in plasma-derived exosomes from melanoma patients and controls. Furthermore, the expression of the three miRNAs may be a promising ancillary tool as a melanoma biomarker, even for discriminating between nevi and melanoma.

Keywords: exosomes; liquid biopsy; melanoma; miRNA; plasma.

Figure 1

Association between tumor stage and microRNA expression. Box-plot of relative expression (log-scale) for hsa-miR-200c-3p, hsa-miR-144-3p, and hsa-miR-221-3p separately for I–II and III–IV stages. The dashed line shows the cutoff on the expression level calculated by the Youden index.

Figure 2

Association between case/control status and microRNA expression. Box-plot of relative expression (log-scale) of hsa-miR-200c-3p, hsa-miR-144-3p, and hsa-miR-221-3 separately for malignant melanoma patients (MM) and patients without melanoma (woM). The dashed line shows the cutoff on the expression level calculated by the Youden index.

Figure 3

Discrimination analysis. ROC curves representing the discrimination ability of hsa-miR-200c-3p, hsa-miR-144-3p, and hsa-miR-221-3p, and the three markers expression combined, distinguishing patients with nevi and patients with melanoma. Accuracy (Acc), sensitivity (Sens), and specificity (Spec) values were obtained using the optimal cutoff point by the Youden index and corrected by optimism through internal validation.