title: Detection of Exosomal miRNAs in the Plasma of Melanoma Patients.
abstract: MicroRNAs (miRNAs) are a class of 22-25 nucleotide RNAs that control gene expression at the post-transcriptional level. MiRNAs have potential as cancer biomarkers. Melanoma is a highly aggressive form of skin cancer accounting for almost 4% of cancers among men and women, and ~80% of skin cancer-related deaths in the US. In the present study we analyzed plasma-derived exosomal miRNAs from clinically affected and unaffected familial melanoma patients (CDKN2A/p16 gene carriers) and compared them with affected (nonfamilial melanoma) and unaffected control subjects in order to identify novel risk biomarkers for melanoma. Intact miRNAs can be isolated from the circulation because of their presence in exosomes. A number of differentially regulated miRNAs identified by NanoString human V2 miRNA array were validated by quantitative PCR. Significantly, miR-17, miR-19a, miR-21, miR-126, and miR-149 were expressed at higher levels in patients with metastatic sporadic melanoma as compared with familial melanoma patients or unaffected control subjects. Surprisingly, no substantial differences in miRNA expression were detected between familial melanoma patients (all inclusive) and unaffected control subjects. The miRNAs differentially expressed in the different patient cohorts, especially in patients with metastatic melanoma, may play important roles in tumor progression and metastasis, and may be used as predictive biomarkers to monitor remission as well as relapse following therapeutic intervention.
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas Street, Memphis, TN 38163, USA. spfeffer@uthsc.edu.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Pfeffer
authors.affiliation: Department of Oncology, University of Utah, Salt Lake City, UT 84112, USA. kenneth.grossmann@hci.utah.edu.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Grossmann
authors.affiliation: Department of Dermatology, Oregon Health &amp; Science University, Portland, OR 97239, USA. cassidyp@ohsu.edu.
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Cassidy
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas Street, Memphis, TN 38163, USA. cyang@uthsc.edu.
authors.forename: Chuan He
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas Street, Memphis, TN 38163, USA. mfan2@uthsc.edu.
authors.forename: Meiyun
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Medicine, Weill Cornell College of Medicine, New York, NY 10065, USA. kopelovichl@gmail.com.
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.affiliation: Department of Dermatology, Oregon Health &amp; Science University, Portland, OR 97239, USA. leachmas@ohsu.edu.
authors.forename: Sancy A
authors.initials: SA
authors.lastname: Leachman
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas Street, Memphis, TN 38163, USA. LPFEFFER@UTHSC.EDU.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Pfeffer
keywords: exosomes; melanoma; metastasis; miRNAs