title: A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis.
abstract: OBJECTIVE
  Brain metastasis is the major cause of mortality among patients with melanoma. A molecular prognostic test that can reliably stratify patients at initial melanoma diagnosis by risk of developing brain metastasis may inform the clinical management of these patients.
  
  
  METHODS
  We performed a retrospective, cohort-based study analyzing genome-wide and targeted microRNA expression profiling of primary melanoma tumors of three patient cohorts (n = 92, 119, and 45) with extensive clinical follow-up. We used Cox regression analysis to establish a microRNA-based signature that improves the ability of the current clinicopathologic staging system to predict the development of brain metastasis.
  
  
  RESULTS
  Our analyses identified a 4-microRNA (miR-150-5p, miR-15b-5p, miR-16-5p, and miR-374b-3p) prognostic signature that, in combination with stage, distinguished primary melanomas that metastasized to the brain from nonrecurrent and non-brain metastatic primary tumors (training cohort: C-index = 81.4%, validation cohort: C-index = 67.4%, independent cohort: C-index = 76.9%). Corresponding Kaplan-Meier curves of high- versus low-risk patients displayed a clear separation in brain metastasis-free and overall survival (training: P < 0.001; P < 0.001, validation: P = 0.033; P = 0.007, independent: P = 0.021; P = 0.022, respectively). Finally, of the microRNA in the prognostic model, we found that the expression of a key lymphocyte miRNA, miR-150-5p, which is less abundant in primary melanomas metastatic to brain, correlated with presence of CD45(+) tumor-infiltrating lymphocytes.
  
  
  CONCLUSIONS
  A prognostic assay based on the described miRNA expression signature combined with the currently used staging criteria may improve accuracy of primary melanoma patient prognoses and aid clinical management of patients, including selection for adjuvant treatment or clinical trials of adjuvant therapies.
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NYU School of Medicine. Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York.
authors.forename: Doug
authors.initials: D
authors.lastname: Hanniford
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Department of Population Health (Biostatistics), NYU School of Medicine, New York, New York.
authors.forename: Judy
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NYU School of Medicine. Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York.
authors.forename: Lisa
authors.initials: L
authors.lastname: Koetz
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NYU School of Medicine. Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York.
authors.forename: Avital
authors.initials: A
authors.lastname: Gaziel-Sovran
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lackaye
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Department of Population Health (Biostatistics), NYU School of Medicine, New York, New York.
authors.forename: Shulian
authors.initials: S
authors.lastname: Shang
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York. Department of Medicine, NYU School of Medicine, New York, New York.
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlick
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Department of Surgery, NYU School of Medicine, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Shapiro
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Department of Surgery, NYU School of Medicine, New York, New York.
authors.forename: Russell
authors.initials: R
authors.lastname: Berman
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NYU School of Medicine. Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York.
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Department of Population Health (Biostatistics), NYU School of Medicine, New York, New York.
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York.
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NYU School of Medicine. Interdisciplinary Melanoma Cooperative Group, NYU Perlmutter Cancer Institute, NYU School of Medicine, New York, New York. eva.hernando-monge@nyumc.org.
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
mesh_terms: D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D009928:Organ Specificity / Q000235:genetics; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs