Serum exosomal microRNAs as potent circulating biomarkers for melanoma

Abstract

Exosomes are small homogenous membrane vesicles that derive from the exocytosis process of cells and can contain DNA, microRNAs (miRNAs), and/or proteins. Characterization of the content profile of exosomes may reflect the state of the cells that release them, and this could be predictive of disease. In this study, to explore the potential biomarkers for melanoma, we isolated serous exosomes from 30 patients with melanoma and 30 healthy individuals using the ultracentrifugation method. Five miRNAs were subsequently detected in each sample by quantitative reverse transcription-PCR: miRNA-532-5p, miRNA-106b, miRNA-200c, miRNA-199a-5p, and miRNA-210. Only the levels of exo-miRNA-532-5p and exo-miRNA-106b differed between the two groups (Z=-4.17 and -4.57, respectively, P<0.0001). When these two miRNAs were evaluated individually and in combination in 95 melanoma patients and 95 healthy individuals serum samples, the area under the receiver operating characteristic curve values were 0.867, 0.820, and 0.936, respectively. Furthermore, in blinded tests of samples from 25 melanoma patients and 25 healthy individuals, this panel of miRNAs identified 23/25 patients with melanoma (92.0% sensitivity) and 22/25 healthy individuals (88.0% sensitivity). Our exo-miRNA panel also distinguished patients with metastasis from those without metastasis, patients with stage I-II disease from those with stage III-IV disease, and patients who had received pembrolizumab treatment from those who were untreated. Overall, these results indicate that serum exosomal miRNAs, especially exo-miRNA-532-5p and exo-miRNA-106b, have the potential to be used for monitoring and/or a diagnosis of melanoma in a clinical setting.

Potential of Exosomal microRNA-200b as Liquid Biopsy Marker in Pancreatic Ductal Adenocarcinoma

“…Multivariate survival analysis identified miR-200b derived from EpCAM-positive serum exosomes as a potentially independent prognostic marker in PDAC. MiR-200b and miR-200c derived from circulating exosomes have already been shown to possess diagnostic and prognostic value in ovarian cancer, lung cancer, colon cancer, prostate cancer, and melanoma [42,[45][46][47][48]. To our knowledge, our study is the first to present the diagnostic and prognostic value of miR-200b and miR-200c in circulating serum exosomes and their respective EpCAM-positive subfraction in PDAC.…”

Exosomes in chronic inflammatory skin diseases and skin tumors

“…The expression levels of miR‐532‐5p and miR‐106b were significantly higher in exosomes collected from the serum of the melanoma patients compared with healthy controls. This study also suggested that miR‐532‐5p and miR‐106b in exosomes can be used to distinguish melanoma patients from healthy individuals, patients with metastasis from non‐metastatic patients and stage I‐II patients from stage III‐IV patients . Another study found miR‐17, miR‐19a, miR‐21, miR‐126 and miR‐149 in exosomes derived from the plasma of metastatic melanoma patients .…”

The power of microRNAs as diagnostic and prognostic biomarkers in liquid biopsies

“…Alegre and co-workers demonstrated that miR-125b levels in exosomes were significantly lower in patients with advanced melanoma compared to disease-free subjects and healthy individuals [108] . Tengda et al [109] demonstrated that miR-532-5p and miR-106b, isolated from serous exosomes as well as from total serum, were able to discriminate patients with melanoma from healthy controls, metastatic patients from those with no metastasis, patients with stage I-II disease from those with stage III-IV, and patients treated with pembrolizumab from untreated ones.…”