title: MicroRNA expression profiles associated with mutational status and survival in malignant melanoma.
abstract: Malignant cutaneous melanoma is a highly aggressive form of skin cancer. Despite improvements in early melanoma diagnosis, the 5-year survival rate remains low in advanced disease. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment. In this study, we aimed to improve our understanding of microRNA (miRNA) deregulation in melanoma development and their impact on patient survival. Global miRNA expression profiles of a set of melanoma lymph node metastases, melanoma cell lines, and melanocyte cultures were determined using Agilent array. Deregulated miRNAs were evaluated in relation with clinical characteristics, patient survival, and mutational status for BRAF and NRAS. Several miRNAs were differentially expressed between melanocytes and melanomas as well as melanoma cell lines. In melanomas, miR-193a, miR-338, and miR-565 were underexpressed in cases with a BRAF mutation. Furthermore, low expression of miR-191 and high expression of miR-193b were associated with poor melanoma-specific survival. In conclusion, our findings show miRNA dysregulation in malignant melanoma and its relation to established molecular backgrounds of BRAF and NRAS oncogenic mutations. The identification of an miRNA classifier for poor survival may lead to the development of miRNA detection as a complementary prognostic tool in clinical practice.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. stefano.caramuta@ki.se
authors.forename: Stefano
authors.initials: S
authors.lastname: Caramuta
authors.forename: Suzanne
authors.initials: S
authors.lastname: Egyházi
authors.forename: Monica
authors.initials: M
authors.lastname: Rodolfo
authors.forename: Daniela
authors.initials: D
authors.lastname: Witten
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008544:Melanocytes / Q000502:physiology; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D055815:Young Adult
chemical_list: C546818:MIRN193 microRNA, human; C532050:MIRN338 microRNA, human; C546819:MIRN365 microRNA, human; D035683:MicroRNAs; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf