Sánchez-Sendra Beatriz, González-Muñoz José F, Pérez-Debén Silvia, Monteagudo Carlos
Department of Pathology, University of Valencia, 46010 Valencia, Spain.
Biomedical Research Institute INCLIVA, 46010 Valencia, Spain.
Cancers (Basel). 2022 Mar 16;14(6):1532. doi: 10.3390/cancers14061532.
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.
BRAF突变存在于约50%的皮肤恶性黑色素瘤中,并且与晚期黑色素瘤患者的不良预后相关。微小RNA(miRNA)是表观遗传调节因子,可调节癌症中的不同细胞过程,包括黑色素瘤的发生和发展。然而,目前尚无关于原发性皮肤黑色素瘤中BRAF基因的基因改变与miRNA表达之间潜在关联的研究。在此,为了分析BRAF突变对所选miRNA在诊断时预测临床结局和患者生存能力的影响,我们研究了新鲜冷冻的原发性肿瘤标本中miR-125b、miR-200c和miR-205表达的预后价值,其取决于BRAF突变状态。为此,提取RNA用于通过桑格测序研究BRAF突变和miRNA表达。我们的结果表明,尽管在BRAF突变组中它们的预测能力似乎略有偏好,但这三种miRNA的表达可有效地独立于原发性肿瘤诊断时的BRAF突变状态来预测黑色素瘤患者的临床结局。