The Prognostic Value of miR-125b, miR-200c and miR-205 in Primary Cutaneous Malignant Melanoma Is Independent of BRAF Mutational Status

SIMPLE SUMMARY: Melanoma accounts for the majority of skin cancer-related deaths. On the one hand, most melanomas contain mutations in the BRAF gene (predominantly V600E), and on the other hand, miRNAs modulate different steps in melanoma development and progression, but there are no reports that study the relation between BRAF mutational status and the expression of miRNAs, which is important for an accurate patient prognosis. The aim of our retrospective study was to know whether BRAF mutations influence the prognostic value of miR-125b, miR-200c and miR-205 intratumoral expression in primary cutaneous melanomas. Globally, our results showed that miR-125b, miR-200c and miR-205 expression predicted the clinical outcome of primary melanomas independently of BRAF status. Thus, our findings support that BRAF mutations alone do not predict the risk of metastasis development or melanoma survival and that miR-125b, miR-200c and miR-205 may be considered as accurate prognostic biomarkers in melanoma regardless of BRAF mutational status. ABSTRACT: BRAF mutations are present in around 50% of cutaneous malignant melanomas and are related to a poor outcome in advanced-stage melanoma patients. miRNAs are epigenetic regulators that modulate different cellular processes in cancer, including melanoma development and progression. However, there are no studies on the potential associations of the genetic alterations of the BRAF gene with miRNA expression in primary cutaneous melanomas. Here, in order to analyze the influence of BRAF mutations in the ability of selected miRNAs to predict clinical outcome and patient survival at the time of diagnosis, we studied the prognostic value of miR-125b, miR-200c and miR-205 expression depending on the BRAF mutational status in fresh, frozen primary tumor specimens. For this purpose, RNA was extracted for studying both BRAF mutations by Sanger sequencing and miRNA expression. Our results indicate that, although there seems to be a slight preference for their predictive ability in the BRAF mutated group, the expression of these three miRNAs serves effectively to predict the clinical outcome of melanoma patients independently of BRAF mutational status at the time of primary tumor diagnosis.