Journal article
MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma
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.
| Language: | English |
|---|---|
| Year: | 2014 |
| Pages: | 541-549 |
| ISSN: | 17553768 and 1755375x |
| Types: | Journal article |
| DOI: | 10.1111/aos.12322 |
| ORCIDs: | 0000-0003-1941-2681 , 0000-0001-8697-0734 , 0000-0003-1054-1460 and Winther, Ole |
03502, Genetics - General 03508, Genetics - Human 12502, Pathology - General 20006, Sense organs - Pathology 24004, Neoplasms - Pathology, clinical aspects and systemic effects 24500, Gerontology Biochemistry and Molecular Biophysics CHOROIDAL MELANOMAS CHROMOSOME-3 CILIARY BODY CONJUNCTIVAL MALIGNANT-MELANOMA Chromosomal aberrations Cox regression analysis mathematical and computer techniques DENMARK DISEASE Expression FOLLOW-UP Genetic Genetics Human Medicine, Medical Sciences MESSENGER RNA MONOSOMY 3 Metastasis Methods and Techniques MicroRNA Molecular Genetics Multiplex ligation-dependent probe Multiplex ligation-dependent probe amplification OPHTHALMOLOGY Oncology Ophthalmology PROGNOSTIC-FACTORS 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 Prognostic factors SDG 3 - Good Health and Well-being SURVIVAL Survival Uveal melanoma amplifteation chromosomal aberrations chromosome 1 1p chromosome 3 chromosome 8 8q expression genetic hierarchical clustering mathematical and computer techniques metastasis metastasis neoplastic disease mortality microRNA microRNA miRNA expression multiplex ligation-dependent probe amplification MLPA laboratory techniques, genetic techniques prognosis prognostic factors survival uveal melanoma Melanoma (MeSH) Uveal Neoplasms (MeSH) neoplastic disease, eye disease pathology, mortality uvtial melanoma
Adult Aged Aged, 80 and over Chromosome Aberrations Chromosomes, Human, Pair 3 Chromosomes, Human, Pair 8 Female Gene Expression Profiling Humans Lymphatic Metastasis Male Melanoma MicroRNAs Middle Aged Multiplex Polymerase Chain Reaction Neoplasm Proteins Proportional Hazards Models Survival Rate Uveal Neoplasms uveal melanoma
