title: MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors.
abstract: Objective: 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.Research design and methods: 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.Results: 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 inBRAF-mutated patients. Moreover, high expression of miR-192 and miR-193b* and low expression of miR-132 resulted in significant association with shorter progression.Conclusion: 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.
authors.affiliation: 1IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory , Bari , Italy +0039 0805555283 ; s.tommasi@oncologico.bari.it.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Pinto
authors.forename: Sabino
authors.initials: S
authors.lastname: Strippoli
authors.forename: Simona
authors.initials: S
authors.lastname: De Summa
authors.forename: Anna
authors.initials: A
authors.lastname: Albano
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guida
authors.forename: Ondina
authors.initials: O
authors.lastname: Popescu
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Michele
authors.initials: M
authors.lastname: Guida
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi