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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 a...
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| Published in: | Acta ophthalmologica (Oxford, England) England), 2014-09, Vol.92 (6), p.541-549 |
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| container_title | Acta ophthalmologica (Oxford, England) |
| container_volume | 92 |
| creator | Larsen, Ann‐Cathrine Holst, Line Kaczkowski, Bogumil Andersen, Morten T. Manfé, Valentina Siersma, Volkert D. Kolko, Miriam Kiilgaard, Jens F. Winther, Ole Prause, Jan U. Gniadecki, Robert Heegaard, Steffen |
| description | 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 |
| doi_str_mv | 10.1111/aos.12322 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1553712028</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3402909741</sourcerecordid><originalsourceid>FETCH-LOGICAL-p3492-754a2f6bd6c6bfdb5f785f630a1069c3760d770ff0218fd5b9bd749fe0db19093</originalsourceid><addsrcrecordid>eNpdkbtOwzAUhi0EoqUw8AIoEgtLW19iOxkrxE1qqcRFYouc2EaunAtxAu3Gws4z8iSYtFQILz72__no-P8BOEZwhPwai9KNECYY74A-4pQOCWfR7ramTz1w4NwCQoYYC_dBD4eEk5DGffAxM1ld3t1OArWsauWcKYtAFMKunHG-kMGstY2prFoG1jyLxutf759SVaqQqmiCqi5TFYi8skabrNMDUwS5aoRr_DHrmhTdqz-X7asS1lNWFGUuDsGeFtapo80-AI-XFw_n18Pp_OrmfDIdViSM8ZDTUGDNUskylmqZUs0jqhmBAkEWZ_7XUHIOtYYYRVrSNE4lD2OtoExRDGMyAGfrvn7ql1a5JsmNy5T1U6iydQmilHCEIY48evoPXZRt7Y1ZU97tkENPnWyoNs2VTKra5KJeJb8Ge2C8Bt6MVautjmDyk1zik0u65JLJ_L4ryDegeI81</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1553232470</pqid></control><display><type>article</type><title>MicroRNA expression analysis and Multiplex ligation‐dependent probe amplification in metastatic and non‐metastatic uveal melanoma</title><source>Wiley-Blackwell Journals</source><creator>Larsen, Ann‐Cathrine ; Holst, Line ; Kaczkowski, Bogumil ; Andersen, Morten T. ; Manfé, Valentina ; Siersma, Volkert D. ; Kolko, Miriam ; Kiilgaard, Jens F. ; Winther, Ole ; Prause, Jan U. ; Gniadecki, Robert ; Heegaard, Steffen</creator><creatorcontrib>Larsen, Ann‐Cathrine ; Holst, Line ; Kaczkowski, Bogumil ; Andersen, Morten T. ; Manfé, Valentina ; Siersma, Volkert D. ; Kolko, Miriam ; Kiilgaard, Jens F. ; Winther, Ole ; Prause, Jan U. ; Gniadecki, Robert ; Heegaard, Steffen</creatorcontrib><description>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.</description><identifier>ISSN: 1755-375X</identifier><identifier>EISSN: 1755-3768</identifier><identifier>DOI: 10.1111/aos.12322</identifier><identifier>PMID: 24373459</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; chromosomal aberrations ; Chromosome Aberrations ; Chromosomes, Human, Pair 3 - genetics ; Chromosomes, Human, Pair 8 - genetics ; expression ; Female ; Gene Expression Profiling ; genetic ; Humans ; Lymphatic Metastasis ; Male ; Melanoma - genetics ; Melanoma - mortality ; Melanoma - secondary ; metastasis ; microRNA ; MicroRNAs - genetics ; Middle Aged ; Multiplex ligation‐dependent probe amplification ; Multiplex Polymerase Chain Reaction ; Neoplasm Proteins - genetics ; Ophthalmology ; prognostic factors ; Proportional Hazards Models ; survival ; Survival Rate ; uveal melanoma ; Uveal Neoplasms - genetics ; Uveal Neoplasms - mortality ; Uveal Neoplasms - pathology</subject><ispartof>Acta ophthalmologica (Oxford, England), 2014-09, Vol.92 (6), p.541-549</ispartof><rights>2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd</rights><rights>2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2014 Acta Ophthalmologica Scandinavica Foundation</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Faos.12322$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Faos.12322$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24373459$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Larsen, Ann‐Cathrine</creatorcontrib><creatorcontrib>Holst, Line</creatorcontrib><creatorcontrib>Kaczkowski, Bogumil</creatorcontrib><creatorcontrib>Andersen, Morten T.</creatorcontrib><creatorcontrib>Manfé, Valentina</creatorcontrib><creatorcontrib>Siersma, Volkert D.</creatorcontrib><creatorcontrib>Kolko, Miriam</creatorcontrib><creatorcontrib>Kiilgaard, Jens F.</creatorcontrib><creatorcontrib>Winther, Ole</creatorcontrib><creatorcontrib>Prause, Jan U.</creatorcontrib><creatorcontrib>Gniadecki, Robert</creatorcontrib><creatorcontrib>Heegaard, Steffen</creatorcontrib><title>MicroRNA expression analysis and Multiplex ligation‐dependent probe amplification in metastatic and non‐metastatic uveal melanoma</title><title>Acta ophthalmologica (Oxford, England)</title><addtitle>Acta Ophthalmol</addtitle><description>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.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>chromosomal aberrations</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes, Human, Pair 3 - genetics</subject><subject>Chromosomes, Human, Pair 8 - genetics</subject><subject>expression</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>genetic</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Melanoma - genetics</subject><subject>Melanoma - mortality</subject><subject>Melanoma - secondary</subject><subject>metastasis</subject><subject>microRNA</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Multiplex ligation‐dependent probe amplification</subject><subject>Multiplex Polymerase Chain Reaction</subject><subject>Neoplasm Proteins - genetics</subject><subject>Ophthalmology</subject><subject>prognostic factors</subject><subject>Proportional Hazards Models</subject><subject>survival</subject><subject>Survival Rate</subject><subject>uveal melanoma</subject><subject>Uveal Neoplasms - genetics</subject><subject>Uveal Neoplasms - mortality</subject><subject>Uveal Neoplasms - pathology</subject><issn>1755-375X</issn><issn>1755-3768</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNpdkbtOwzAUhi0EoqUw8AIoEgtLW19iOxkrxE1qqcRFYouc2EaunAtxAu3Gws4z8iSYtFQILz72__no-P8BOEZwhPwai9KNECYY74A-4pQOCWfR7ramTz1w4NwCQoYYC_dBD4eEk5DGffAxM1ld3t1OArWsauWcKYtAFMKunHG-kMGstY2prFoG1jyLxutf759SVaqQqmiCqi5TFYi8skabrNMDUwS5aoRr_DHrmhTdqz-X7asS1lNWFGUuDsGeFtapo80-AI-XFw_n18Pp_OrmfDIdViSM8ZDTUGDNUskylmqZUs0jqhmBAkEWZ_7XUHIOtYYYRVrSNE4lD2OtoExRDGMyAGfrvn7ql1a5JsmNy5T1U6iydQmilHCEIY48evoPXZRt7Y1ZU97tkENPnWyoNs2VTKra5KJeJb8Ge2C8Bt6MVautjmDyk1zik0u65JLJ_L4ryDegeI81</recordid><startdate>201409</startdate><enddate>201409</enddate><creator>Larsen, Ann‐Cathrine</creator><creator>Holst, Line</creator><creator>Kaczkowski, Bogumil</creator><creator>Andersen, Morten T.</creator><creator>Manfé, Valentina</creator><creator>Siersma, Volkert D.</creator><creator>Kolko, Miriam</creator><creator>Kiilgaard, Jens F.</creator><creator>Winther, Ole</creator><creator>Prause, Jan U.</creator><creator>Gniadecki, Robert</creator><creator>Heegaard, Steffen</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>201409</creationdate><title>MicroRNA expression analysis and Multiplex ligation‐dependent probe amplification in metastatic and non‐metastatic uveal melanoma</title><author>Larsen, Ann‐Cathrine ; Holst, Line ; Kaczkowski, Bogumil ; Andersen, Morten T. ; Manfé, Valentina ; Siersma, Volkert D. ; Kolko, Miriam ; Kiilgaard, Jens F. ; Winther, Ole ; Prause, Jan U. ; Gniadecki, Robert ; Heegaard, Steffen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3492-754a2f6bd6c6bfdb5f785f630a1069c3760d770ff0218fd5b9bd749fe0db19093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>chromosomal aberrations</topic><topic>Chromosome Aberrations</topic><topic>Chromosomes, Human, Pair 3 - genetics</topic><topic>Chromosomes, Human, Pair 8 - genetics</topic><topic>expression</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>genetic</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Melanoma - genetics</topic><topic>Melanoma - mortality</topic><topic>Melanoma - secondary</topic><topic>metastasis</topic><topic>microRNA</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>Multiplex ligation‐dependent probe amplification</topic><topic>Multiplex Polymerase Chain Reaction</topic><topic>Neoplasm Proteins - genetics</topic><topic>Ophthalmology</topic><topic>prognostic factors</topic><topic>Proportional Hazards Models</topic><topic>survival</topic><topic>Survival Rate</topic><topic>uveal melanoma</topic><topic>Uveal Neoplasms - genetics</topic><topic>Uveal Neoplasms - mortality</topic><topic>Uveal Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Larsen, Ann‐Cathrine</creatorcontrib><creatorcontrib>Holst, Line</creatorcontrib><creatorcontrib>Kaczkowski, Bogumil</creatorcontrib><creatorcontrib>Andersen, Morten T.</creatorcontrib><creatorcontrib>Manfé, Valentina</creatorcontrib><creatorcontrib>Siersma, Volkert D.</creatorcontrib><creatorcontrib>Kolko, Miriam</creatorcontrib><creatorcontrib>Kiilgaard, Jens F.</creatorcontrib><creatorcontrib>Winther, Ole</creatorcontrib><creatorcontrib>Prause, Jan U.</creatorcontrib><creatorcontrib>Gniadecki, Robert</creatorcontrib><creatorcontrib>Heegaard, Steffen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta ophthalmologica (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Larsen, Ann‐Cathrine</au><au>Holst, Line</au><au>Kaczkowski, Bogumil</au><au>Andersen, Morten T.</au><au>Manfé, Valentina</au><au>Siersma, Volkert D.</au><au>Kolko, Miriam</au><au>Kiilgaard, Jens F.</au><au>Winther, Ole</au><au>Prause, Jan U.</au><au>Gniadecki, Robert</au><au>Heegaard, Steffen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA expression analysis and Multiplex ligation‐dependent probe amplification in metastatic and non‐metastatic uveal melanoma</atitle><jtitle>Acta ophthalmologica (Oxford, England)</jtitle><addtitle>Acta Ophthalmol</addtitle><date>2014-09</date><risdate>2014</risdate><volume>92</volume><issue>6</issue><spage>541</spage><epage>549</epage><pages>541-549</pages><issn>1755-375X</issn><eissn>1755-3768</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>24373459</pmid><doi>10.1111/aos.12322</doi><tpages>9</tpages></addata></record> |
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| ispartof | Acta ophthalmologica (Oxford, England), 2014-09, Vol.92 (6), p.541-549 |
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| source | Wiley-Blackwell Journals |
| subjects | Adult Aged Aged, 80 and over chromosomal aberrations Chromosome Aberrations Chromosomes, Human, Pair 3 - genetics Chromosomes, Human, Pair 8 - genetics expression Female Gene Expression Profiling genetic Humans Lymphatic Metastasis Male Melanoma - genetics Melanoma - mortality Melanoma - secondary metastasis microRNA MicroRNAs - genetics Middle Aged Multiplex ligation‐dependent probe amplification Multiplex Polymerase Chain Reaction Neoplasm Proteins - genetics Ophthalmology prognostic factors Proportional Hazards Models survival Survival Rate uveal melanoma Uveal Neoplasms - genetics Uveal Neoplasms - mortality Uveal Neoplasms - pathology |
| title | MicroRNA expression analysis and Multiplex ligation‐dependent probe amplification in metastatic and non‐metastatic uveal melanoma |
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