title: MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis.
abstract: The role of microRNAs (miRNAs) in melanoma is unclear. We examined global miRNA expression profiles in fresh-frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, with validation in independent cohorts of tumours and sera. We integrated miRNA and mRNA information from the same samples and elucidated networks associated with outcome and mutation. Associations with prognosis were replicated for miR-150-5p, miR-142-3p and miR-142-5p. Co-analysis of miRNA and mRNA uncovered a network associated with poor prognosis (PP) that paradoxically favoured expression of miRNAs opposing tumorigenesis. These miRNAs are likely part of an autoregulatory response to oncogenic drivers, rather than drivers themselves. Robust association of miR-150-5p and the miR-142 duplex with good prognosis and earlier stage metastatic melanoma supports their potential as biomarkers. miRNAs overexpressed in association with PP in an autoregulatory fashion will not be suitable therapeutic targets.
authors.affiliation: Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Varsha
authors.initials: V
authors.lastname: Tembe
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Schramm
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Stark
authors.forename: Ellis
authors.initials: E
authors.lastname: Patrick
authors.forename: Vivek
authors.initials: V
authors.lastname: Jayaswal
authors.forename: Yue Hang
authors.initials: YH
authors.lastname: Tang
authors.forename: Andrew
authors.initials: A
authors.lastname: Barbour
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Yee Hwa
authors.initials: YH
authors.lastname: Yang
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
mesh_terms: D015331:Cohort Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D000096142:Cutaneous Malignant Melanoma
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; bioinformatics; biomarker; melanoma; miRNA; microRNA; network; pathology; prognosis