MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma

Ann-Cathrine Larsen, Line Holst, Bogumil Kaczkowski, Morten T. Andersen, Valentina Manfe, Volkert D. Siersma, Miriam Kolko, Jens F. Kiilgaard, Ole Winther, Jan U. Prause, Robert Gniadecki, Steffen Heegaard

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Purpose: To determine the association of microRNA expression and chromosomal changes with metastasis and survival in uveal melanoma (UM). Methods: Thirty-six patients with UM were selected based on the metastatic status, and clinicopathological data were collected. Multiplex ligation-dependent probe amplification (MLPA) was used to identify chromosomal changes. Chromosomal changes and clinicopathological data were correlated with survival and metastasis. The microRNA expression was analysed in 26 of the 36 archived UM samples. Unsupervised analysis, differential expression analysis and Cox regression analysis were performed to determine the association with metastasis and survival. Results: Metastasis and metastatic death occurred in 20 patients, two patients died of other causes and one patient of unknown causes. A significant association between increasing size category (p = 0.002, log-rank), extraocular extension (p = 0.001), chromosome 3 loss (p = 0.033) and lp loss (p = 0.030) and development of metastases was observed. Tumour, node, metastasis (TNM) staging showed a significant association with survival (p <0.0001, log-rank). Adjusting for gender and age TNM size category T4 (p = 0.016, Cox regression analysis), mixed (p = 0.029) and epithelioid (p = 0.0058) cell types, chromosome 3 loss (p 0.014) and 8q gain (p = 0.010) were significant prognosticators for a poor survival. Hierarchical clustering divided the UM into three groups based on microRNA expression. The clusters showed no association with clinical or histopathological features, TNM staging, metastasis or survival. Differential expression analysis did not reveal microRNAs related to metastasis or survival. Conclusions: The prognostic significance of chromosome 3 loss and 8q gain identified by MLPA analysis was confirmed in archived UM samples. The value of microRNA expression as a predictor of metastasis and survival in UM could not be confirmed.
Original languageEnglish
JournalActa Ophthalmologica
Issue number6
Pages (from-to)541-549
Publication statusPublished - 2014


  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common adult, aged, aged/80 and over, middle age female, male
  • microRNA miRNA expression
  • 03502, Genetics - General
  • 03508, Genetics - Human
  • 12502, Pathology - General
  • 20006, Sense organs - Pathology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 24500, Gerontology
  • Genetics
  • Methods and Techniques
  • Molecular Genetics
  • Oncology
  • Ophthalmology
  • metastasis neoplastic disease mortality
  • uveal melanoma Melanoma (MeSH) Uveal Neoplasms (MeSH) neoplastic disease, eye disease pathology, mortality
  • prognosis
  • Biochemistry and Molecular Biophysics
  • Human Medicine, Medical Sciences
  • chromosome 1 1p
  • chromosome 3
  • chromosome 8 8q
  • Cox regression analysis mathematical and computer techniques
  • hierarchical clustering mathematical and computer techniques
  • multiplex ligation-dependent probe amplification MLPA laboratory techniques, genetic techniques
  • chromosomal aberrations
  • expression
  • genetic
  • metastasis
  • microRNA
  • Multiplex ligation-dependent probe
  • amplifteation
  • prognostic factors
  • survival
  • uvtial melanoma
  • Chromosomal aberrations
  • Expression
  • Genetic
  • Metastasis
  • MicroRNA
  • Multiplex ligation-dependent probe amplification
  • Prognostic factors
  • Survival
  • Uveal melanoma


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