title: Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients.
abstract: BACKGROUND
  Identification of primary melanoma patients at the highest risk of recurrence remains a critical challenge, and monitoring for recurrent disease is limited to costly imaging studies. We recently reported our array-based discovery of prognostic serum miRNAs in melanoma. In the current study, we examined the clinical utility of these serum-based miRNAs for prognosis as well as detection of melanoma recurrence.
  
  
  METHODS
  Serum levels of 12 miRNAs were tested using qRT-PCR at diagnosis in 283 melanoma patients (training cohort, n = 201; independent validation, n = 82; median follow-up, 68.8 months). A refined miRNA signature was chosen and evaluated. We also tested the potential clinical utility of the miRNAs in early detection and monitoring of recurrence using multiple longitudinal samples (pre- and postrecurrence) in a subset of 82 patients (n = 225). In addition, we integrated our miRNA signature with publicly available Cancer Genome Atlas data to examine the relevance of these miRNAs to melanoma biology.
  
  
  RESULTS
  Four miRNAs (miR-150, miR-30d, miR-15b, and miR-425) in combination with stage separated patients by recurrence-free survival (RFS) and overall survival (OS) and improved prediction of recurrence over stage alone in both the training and validation cohorts (training RFS and OS, P < .001; validation RFS, P < .001; OS, P = .005). Serum miR-15b levels significantly increased over time in recurrent patients (P < .001), adjusting for endogenous controls as well as age, sex, and initial stage. In nonrecurrent patients, miR-15b levels were not significantly changed with time (P =.17).
  
  
  CONCLUSIONS
  Data demonstrate that serum miRNAs can improve melanoma patient stratification over stage and support further testing of miR-15b to guide patient surveillance.
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York; Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, New York.
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Fleming
authors.forename: Judy
authors.initials: J
authors.lastname: Zhong
authors.forename: Inês Pires
authors.initials: IP
authors.lastname: da Silva
authors.forename: Eleazar
authors.initials: E
authors.lastname: Vega-Saenz de Miera
authors.forename: Bobbi
authors.initials: B
authors.lastname: Brady
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Han
authors.forename: Doug
authors.initials: D
authors.lastname: Hanniford
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D049690:History, Ancient; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: C505361:MIRN15 microRNA, human; D035683:MicroRNAs
keywords: biomarkers; melanoma; microRNAs; recurrence; serum markers