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.
Screening for prognostic biomarkers is crucial for clinical melanoma management. Insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) has emerged as a potential melanoma diagnostic and prognostic biomarker. It is commonly tested by immunohistochemistry (IHC). Our study retrospectively examines IGF2BP3 mRNA and protein expression in primary melanomas, their correlation with clinicopathologic factors, clinical outcome, and selected miRNAs expression, and their efficiency in predicting melanoma progression and survival. RT-qPCR and IHC on IGF2BP3 expression were performed in 61 cryopreserved and 63 formalin-fixed paraffin-embedded primary melanomas, respectively, and correlated to clinicopathologic factors, distant metastasis-free survival (DMFS), and melanoma -specific survival (MSS). The correlation between RT-qPCR and IHC was significant but moderate. IGF2BP3 mRNA showed a stronger association with clinicopathologic factors (Breslow thickness, ulceration, mitosis rate, growth phase, development of metastasis, and melanoma-specific survival) than its protein counterpart. Interestingly, higher IGF2BP3 mRNA expression was detected in primary melanomas that further metastasized to distant sites and was an independent prognostic factor for the risk of unfavorable DMFS and MSS. RT-qPCR outperformed IHC in sensitivity and in predicting worse clinical outcomes. Therefore, RT-qPCR may successfully be implemented for routine IGF2BP3 assessing for the selection of melanoma patients with a higher risk of developing distant metastasis and dying of melanoma.
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