The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

Abstract

Uveal melanoma (UM) is the most common primary tumor of the eye diagnosed in adults, associated with a high risk of metastasis and thereby, poor prognosis. Among known risk factors for the development of metastatic disease is the loss of BAP1 expression and chromosome 3 monosomy in the primary tumor. However, the expression levels of specific micro RNAs (miRNA) in tumor tissue may also serve as a valuable marker for determining the risk of metastatic disease in patients with primary uveal melanoma. In our study, we analyzed the miRNA expression data of cases selected from The Cancer Genome Atlas study on uveal melanoma, and determined a panel of 15 miRNAs differentially expressed between patients with primary and metastatic disease. Next, 6 miRNAs were validated on a group of 46 tumor samples from primary and metastatic patients. We have shown, that expression of hsa-miR-592, hsa-miR-346, and hsa-miR-1247 was significantly increased, while hsa-miR-506 and hsa-miR-513c were decreased in the tumors of patients with metastatic disease. Hsa-miR-196b expression did not differ between the two subgroups, however, we showed significant correlation with BAP1 expression. Moreover, hsa-miR-592 also showed correlation with monosomy 3 tumors. Gene ontology analysis revealed involvement of those miRNAs with cellular processes mediating the metastatic process. Our results showed that miRNAs play an important role in the deregulation of several oncogenic pathways in UM and can, thereby, promote metastatic spread to distant organs. Moreover, differentially expressed miRNAs may be used as an interesting biomarker for the assessment of metastatic risk in uveal melanoma patients.

MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

“…They identified a panel of 15 miRNAs differentially expressed between four TCGA-UM study patients (stage IIA tumours and without metastatic disease) and four TCGA-UM patients (stage IV with metastatic disease). Further validation of six of the miRNAs in 28 primary UM with no evidence of metastasis and 18 primary UM, where metastatic disease had developed at the time of follow-up, demonstrated that miR-592, miR-346 and miR-1247 were significantly increased, and that miR-506 and miR-513c were significantly decreased in the metastatic subgroup [80].…”

“…A similar approach was taken by Wróblewska et al, but this time combining TCGA miRNA data with miRNA validation in patient samples [80]. They identified a panel of 15 miRNAs differentially expressed between four TCGA-UM study patients (stage IIA tumours and without metastatic disease) and four TCGA-UM patients (stage IV with metastatic disease).…”

The Analysis of Inflammation-Related Proteins in a Cargo of Exosomes Derived from the Serum of Uveal Melanoma Patients Reveals Potential Biomarkers of Disease Progression

“…In our previous study, we reported the possible use of miRNAs differentially expressed in UM tumours as biomarkers for the assessment of metastatic risk in uveal melanoma patients [69]. In this study, we present the first analysis of inflammatory-related protein cargo of exosomes derived from the serum of healthy donors and uveal melanoma patients with primary and metastatic disease.…”

The Role of Non-Coding RNAs in Uveal Melanoma

“…Results corresponded to either elevated (miR-592, miR-346, and miR-1247) or decreased (miR-506 and miR-513c) expression in the metastatic stage. miR-196b did not show quantitative differences in its expression, but was correlated with the expression of BAP1 [ 65 ]. In histological samples, Radhakrishnan and coworkers related chromosomal alterations of pairs 1, 3, and 8 with miRNA expression according to whether the samples belonged to tumors that had developed liver metastases or not [ 66 ].…”