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

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Abstract

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.

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 OPHTHALMOLOGY CONJUNCTIVAL MALIGNANT-MELANOMA CILIARY BODY CHOROIDAL MELANOMAS PROGNOSTIC-FACTORS MONOSOMY 3 FOLLOW-UP SURVIVAL CHROMOSOME-3 DISEASE DENMARK chromosomal aberrations expression genetic metastasis microRNA Multiplex ligation-dependent probe amplifteation prognostic factors survival uvtial melanoma MESSENGER RNA Chromosomal aberrations Expression Genetic Metastasis MicroRNA Multiplex ligation-dependent probe amplification Prognostic factors Survival Uveal melanoma