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Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy: a DBCG study
Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients trea...
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Published in: | PloS one 2012-05, Vol.7 (5), p.e36170-e36170 |
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description | Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence.
Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics.
Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics. |
doi_str_mv | 10.1371/journal.pone.0036170 |
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Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics.
Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0036170</identifier><identifier>PMID: 22623953</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvant chemotherapy ; Antineoplastic Agents, Hormonal - therapeutic use ; Biology ; Biomarkers ; Breast ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cancer ; Cancer patients ; Cancer research ; Cancer therapies ; Cluster Analysis ; Clustering ; Development and progression ; Endocrine therapy ; Epidermal growth factor ; Estrogen ; Estrogen receptors ; Estrogens ; Experimental design ; Female ; Gene expression ; Gene Expression Profiling ; Health aspects ; Health risks ; Histopathology ; Hospitals ; Humans ; Insulin-like growth factors ; Medical diagnosis ; Medical prognosis ; Medicine ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Parameter identification ; Patients ; Phosphorylation ; Physics ; Quality ; Receptors, Estrogen - metabolism ; Ribonucleic acid ; Risk factors ; Risk groups ; RNA ; Stem cells ; Studies ; Tamoxifen ; Tamoxifen - metabolism ; Tamoxifen - therapeutic use ; Test sets ; Therapy ; Tumorigenesis ; Tumors</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e36170-e36170</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Lyng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Lyng et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6730-6f6d71aaba28c098b6410d71185cd863e112386659695422071e6d6bee28261d3</citedby><cites>FETCH-LOGICAL-c6730-6f6d71aaba28c098b6410d71185cd863e112386659695422071e6d6bee28261d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1324607791/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1324607791?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22623953$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhang, Lin</contributor><creatorcontrib>Lyng, Maria B</creatorcontrib><creatorcontrib>Lænkholm, Anne-Vibeke</creatorcontrib><creatorcontrib>Søkilde, Rolf</creatorcontrib><creatorcontrib>Gravgaard, Karina H</creatorcontrib><creatorcontrib>Litman, Thomas</creatorcontrib><creatorcontrib>Ditzel, Henrik J</creatorcontrib><title>Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy: a DBCG study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence.
Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics.
Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.</description><subject>Adjuvant chemotherapy</subject><subject>Antineoplastic Agents, Hormonal - therapeutic use</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Breast</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cluster Analysis</subject><subject>Clustering</subject><subject>Development and progression</subject><subject>Endocrine therapy</subject><subject>Epidermal growth factor</subject><subject>Estrogen</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Experimental design</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Histopathology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Insulin-like growth factors</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - 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therapeutic use</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Breast</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cluster Analysis</topic><topic>Clustering</topic><topic>Development and progression</topic><topic>Endocrine therapy</topic><topic>Epidermal growth factor</topic><topic>Estrogen</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Experimental design</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>Histopathology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Insulin-like growth factors</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Parameter identification</topic><topic>Patients</topic><topic>Phosphorylation</topic><topic>Physics</topic><topic>Quality</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Ribonucleic acid</topic><topic>Risk factors</topic><topic>Risk groups</topic><topic>RNA</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Tamoxifen</topic><topic>Tamoxifen - metabolism</topic><topic>Tamoxifen - therapeutic use</topic><topic>Test sets</topic><topic>Therapy</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lyng, Maria B</creatorcontrib><creatorcontrib>Lænkholm, Anne-Vibeke</creatorcontrib><creatorcontrib>Søkilde, Rolf</creatorcontrib><creatorcontrib>Gravgaard, Karina H</creatorcontrib><creatorcontrib>Litman, Thomas</creatorcontrib><creatorcontrib>Ditzel, Henrik J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Science in Context</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence.
Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics.
Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22623953</pmid><doi>10.1371/journal.pone.0036170</doi><tpages>e36170</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvant chemotherapy Antineoplastic Agents, Hormonal - therapeutic use Biology Biomarkers Breast Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Cancer Cancer patients Cancer research Cancer therapies Cluster Analysis Clustering Development and progression Endocrine therapy Epidermal growth factor Estrogen Estrogen receptors Estrogens Experimental design Female Gene expression Gene Expression Profiling Health aspects Health risks Histopathology Hospitals Humans Insulin-like growth factors Medical diagnosis Medical prognosis Medicine MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Parameter identification Patients Phosphorylation Physics Quality Receptors, Estrogen - metabolism Ribonucleic acid Risk factors Risk groups RNA Stem cells Studies Tamoxifen Tamoxifen - metabolism Tamoxifen - therapeutic use Test sets Therapy Tumorigenesis Tumors |
title | Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy: a DBCG study |
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