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

Ann-Cathrine Larsen; Line Marie Holst; Bogumil Kaczkowski; Morten Tolstrup Andersen; Valentina Manfé; Volkert Dirk Siersma; Miriam Kolko; Jens Folke Kiilgaard; Ole Winther; Jan Ulrik Prause; Robert Gniadecki; Steffen Heegaard

doi:10.1111/aos.12322

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

Ann-Cathrine Larsen, Line Marie Holst, Bogumil Kaczkowski, Morten Tolstrup Andersen, Valentina Manfé, Volkert Dirk Siersma, Miriam Kolko, Jens Folke Kiilgaard, Ole Winther, Jan Ulrik Prause, Robert Gniadecki, Steffen Heegaard

21 Citations (Scopus)

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 1p 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 language	English
Journal	Acta Ophthalmologica
Volume	92
Issue number	6
Pages (from-to)	541-549
ISSN	1755-375X
DOIs	https://doi.org/10.1111/aos.12322
Publication status	Published - Sept 2014

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10.1111/aos.12322

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Larsen, A.-C., Holst, L. M., Kaczkowski, B., Andersen, M. T., Manfé, V., Siersma, V. D., Kolko, M., Kiilgaard, J. F., Winther, O., Prause, J. U., Gniadecki, R., & Heegaard, S. (2014). MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma. Acta Ophthalmologica, 92(6), 541-549. https://doi.org/10.1111/aos.12322

Larsen, A-C, Holst, LM, Kaczkowski, B, Andersen, MT, Manfé, V, Siersma, VD , Kolko, M , Kiilgaard, JF , Winther, O, Prause, JU, Gniadecki, R & Heegaard, S 2014, 'MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma', Acta Ophthalmologica, vol. 92, no. 6, pp. 541-549. https://doi.org/10.1111/aos.12322

@article{1b6b1086d9244044b27e4900bf080db2,

title = "MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma",

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 1p 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.",

author = "Ann-Cathrine Larsen and Holst, {Line Marie} and Bogumil Kaczkowski and Andersen, {Morten Tolstrup} and Valentina Manf{\'e} and Siersma, {Volkert Dirk} and Miriam Kolko and Kiilgaard, {Jens Folke} and Ole Winther and Prause, {Jan Ulrik} and Robert Gniadecki and Steffen Heegaard",

year = "2014",

month = sep,

doi = "10.1111/aos.12322",

language = "English",

volume = "92",

pages = "541--549",

journal = "Acta Ophthalmologica",

issn = "1755-375X",

publisher = "Wiley-Blackwell",

number = "6",

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TY - JOUR

T1 - MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma

AU - Larsen, Ann-Cathrine

AU - Holst, Line Marie

AU - Kaczkowski, Bogumil

AU - Andersen, Morten Tolstrup

AU - Manfé, Valentina

AU - Siersma, Volkert Dirk

AU - Kolko, Miriam

AU - Kiilgaard, Jens Folke

AU - Winther, Ole

AU - Prause, Jan Ulrik

AU - Gniadecki, Robert

AU - Heegaard, Steffen

PY - 2014/9

Y1 - 2014/9

N2 - 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 1p 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.

AB - 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 1p 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.

U2 - 10.1111/aos.12322

DO - 10.1111/aos.12322

M3 - Journal article

C2 - 24373459

SN - 1755-375X

VL - 92

SP - 541

EP - 549

JO - Acta Ophthalmologica

JF - Acta Ophthalmologica

IS - 6

ER -

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

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