MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors. (August 2015)

• Record Type: Journal Article
• Authors: Pinto, Rosamaria; Strippoli, Sabino; De Summa, Simona; Albano, Anna; Azzariti, Amalia; Guida, Gabriella; Popescu, Ondina; Lorusso, Vito; Guida, Michele; Tommasi, Stefania
• Is Part Of: Expert opinion on therapeutic targets. Volume 19:Number 8(2015:Aug.)
• Page Start: 1027
• Page End: 1035
• Publication Date: 2015-08
• Subjects: Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1517/14728222.2015.1065818
• Languages: English
• ISSNs: 1744-7631

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Objective:</italic> </bold> Currently, the treatment of BRAF V600-mutated metastatic melanoma with BRAF inhibitors gives a response rate of ∼ 50% with a progression-free survival of ∼ 6 – 7 months. In order to identify predictive biomarkers capable of stratifying BRAF-mutated patients at high risk of shorter response duration to anti-BRAF therapy, the authors analyzed the expression of 15 microRNAs (miRNAs) targeting crucial genes involved in melanoma biology and drug response.</p> <p> <bold> <italic>Research design and methods:</italic> </bold> A total of 15 miRNAs and target gene expression were investigated in 43 patients (30 BRAF-mutated, and 13 BRAF wild-type). Moreover, 20 BRAF-mutated patients treated with vemurafenib were analyzed for miRNA expression in respect to time-to-progression.</p> <p> <bold> <italic>Results:</italic> </bold> All miRNAs except miR-192 showed low expression in BRAF-mutated as compared with BRAF wild-type patients. In particular, miR-101, miR-221, miR-21, miR-338-3p and miR-191 resulted in significant downregulation in BRAF-mutated patients. Moreover, high expression of miR-192 and miR-193b* and low expression of miR-132 resulted in significant association with shorter progression.</p> <p> <bold> <italic>Conclusion:</italic> </bold> Three miRNAs were significantly associated with clinical outcome in metastatic melanoma patients. An increased understanding of the molecular assessment of BRAF-mutated melanomas could allow development of specific molecular tests able to predict response duration.</p> </abstract>