Global MicroRNA Expression Profiling of High-Risk ER+ Breast Cancers from Patients Receiving Adjuvant Tamoxifen Mono-Therapy: A DBCG Study
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{"title"=>"Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant Tamoxifen mono-therapy: A DBCG study", "type"=>"journal", "authors"=>[{"first_name"=>"Maria B.", "last_name"=>"Lyng", "scopus_author_id"=>"18634872500"}, {"first_name"=>"Anne Vibeke", "last_name"=>"Lænkholm", "scopus_author_id"=>"7801324628"}, {"first_name"=>"Rolf", "last_name"=>"Søkilde", "scopus_author_id"=>"35097860300"}, {"first_name"=>"Karina H.", "last_name"=>"Gravgaard", "scopus_author_id"=>"54924506800"}, {"first_name"=>"Thomas", "last_name"=>"Litman", "scopus_author_id"=>"7003926068"}, {"first_name"=>"Henrik J.", "last_name"=>"Ditzel", "scopus_author_id"=>"7004455795"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84862109179", "pmid"=>"22623953", "sgr"=>"84862109179", "doi"=>"10.1371/journal.pone.0036170", "pui"=>"364850185", "isbn"=>"1932-6203"}, "id"=>"fcc89839-55c1-3725-9ab0-164c5c8a8fba", "abstract"=>"PURPOSE: 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.\\n\\nEXPERIMENTAL DESIGN: 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.\\n\\nRESULTS: 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.\\n\\nCONCLUSIONS: 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.", "link"=>"http://www.mendeley.com/research/global-microrna-expression-profiling-highrisk-er-breast-cancers-patients-receiving-adjuvant-tamoxife", "reader_count"=>32, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>15, "Student > Ph. D. Student"=>8, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>15, "Student > Ph. D. Student"=>8, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>11, "Agricultural and Biological Sciences"=>15, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "China"=>1, "Denmark"=>3, "Brazil"=>1, "United Kingdom"=>1, "Spain"=>3}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/635325"], "description"=>"<p>The bold line represents the patients with a good prognosis, whereas the dotted line represents the poor-prognosis patients. A) Probability of recurrence. B) Probability of overall survival.</p>", "links"=>[], "tags"=>["plots", "10", "mirnas"], "article_id"=>305816, "categories"=>["Molecular Biology", "Cell Biology", "Physics", "Biochemistry", "Biophysics", "Biotechnology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Maria B. Lyng", "Anne-Vibeke Lænkholm", "Rolf Søkilde", "Karina H. Gravgaard", "Thomas Litman", "Henrik J. Ditzel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036170.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_plots_of_the_10_miRNAs_identified_in_the_discovery_set_/305816", "title"=>"Kaplan-Meier plots of the 10 miRNAs identified in the discovery set.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-18 01:36:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/635560"], "description"=>"a<p>the average and median were calculated only for the tumors defined as positive, i.e. staining was observed in ≥ 10% of tumor cells by immunohistochemistry.</p>b<p>If the actual percentage was not provided, patients were deemed positive if ER staining was observed in ≥ 10% of tumor cells by immunohistochemistry and/or target protein (ER or PgR) was >10 fmol/mg total protein as determined by biochemistry.</p>c<p>the 5 ER- tumors had a PgR status of 90%, 50%, 90%, 80% and IHC+ (i.e. >10%) respectively.</p><p>Abbreviations: R: patients with recurrence. N: patients without recurrence. Disc.: Discovery set. Test#1: Test set#1. Test#2: Test set#2. Avg: average IDC: invasive ductal carcinoma. ILC: invasive lobular carcinoma. TTR: time to recurrence.</p>", "links"=>[], "tags"=>["included", "patients", "cancer"], "article_id"=>306045, "categories"=>["Molecular Biology", "Cell Biology", "Physics", "Biochemistry", "Biophysics", "Biotechnology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Maria B. Lyng", "Anne-Vibeke Lænkholm", "Rolf Søkilde", "Karina H. Gravgaard", "Thomas Litman", "Henrik J. Ditzel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036170.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_included_patients_and_their_breast_cancer_tumor_N_8202_8202_152_/306045", "title"=>"Characteristics of included patients and their breast cancer tumor (N = 152).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-05-18 01:40:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/330209", "https://ndownloader.figshare.com/files/330257", "https://ndownloader.figshare.com/files/330293", "https://ndownloader.figshare.com/files/330328"], "description"=>"<div><h3>Purpose</h3><p>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.</p> <h3>Experimental Design</h3><p>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.</p> <h3>Results</h3><p>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.</p> <h3>Conclusions</h3><p>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.</p> </div>", "links"=>[], "tags"=>["microrna", "profiling", "high-risk", "cancers", "patients", "receiving", "adjuvant", "tamoxifen", "dbcg"], "article_id"=>125203, "categories"=>["Molecular Biology", "Cell Biology", "Physics", "Biochemistry", "Biophysics", "Biotechnology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Maria B. Lyng", "Anne-Vibeke Lænkholm", "Rolf Søkilde", "Karina H. Gravgaard", "Thomas Litman", "Henrik J. Ditzel"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0036170.s001", "https://dx.doi.org/10.1371/journal.pone.0036170.s002", "https://dx.doi.org/10.1371/journal.pone.0036170.s003", "https://dx.doi.org/10.1371/journal.pone.0036170.s004"], "stats"=>{"downloads"=>6, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Global_MicroRNA_Expression_Profiling_of_High_Risk_ER_Breast_Cancers_from_Patients_Receiving_Adjuvant_Tamoxifen_Mono_Therapy_A_DBCG_Study/125203", "title"=>"Global MicroRNA Expression Profiling of High-Risk ER+ Breast Cancers from Patients Receiving Adjuvant Tamoxifen Mono-Therapy: A DBCG Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-05-18 01:26:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/635215"], "description"=>"<p>Data is based on the discovery set (p<6.6e-4, FDR 2.5% and variance >0.1). The green symbols above the heat-map indicate samples from patients with no recurrence, whereas the red symbols indicate samples from patients with recurrence. The heat-map is a standardized intensity plot with the intensities ranging from −2 (green) to +2 (red).</p>", "links"=>[], "tags"=>["differentially", "mirnas", "adjuvant", "tamoxifen"], "article_id"=>305698, "categories"=>["Molecular Biology", "Cell Biology", "Physics", "Biochemistry", "Biophysics", "Biotechnology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Maria B. Lyng", "Anne-Vibeke Lænkholm", "Rolf Søkilde", "Karina H. Gravgaard", "Thomas Litman", "Henrik J. Ditzel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036170.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_map_of_significantly_differentially_expressed_miRNAs_associated_with_outcome_after_adjuvant_Tamoxifen_treatment_/305698", "title"=>"Heat-map of significantly differentially expressed miRNAs associated with outcome after adjuvant Tamoxifen treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-18 01:34:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/635482"], "description"=>"<p>Grade 1 vs. 3 and Grade 2 vs. 3: p = 0.01, and Grade 1 vs. 2: p = 0.02). N = 52 patients (Discovery set).</p>", "links"=>[], "tags"=>["mir-7"], "article_id"=>305975, "categories"=>["Molecular Biology", "Cell Biology", "Physics", "Biochemistry", "Biophysics", "Biotechnology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Maria B. Lyng", "Anne-Vibeke Lænkholm", "Rolf Søkilde", "Karina H. Gravgaard", "Thomas Litman", "Henrik J. Ditzel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036170.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_miR_7_with_tumor_grade_/305975", "title"=>"Association of miR-7 with tumor grade.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-18 01:39:35"}

PMC Usage Stats | Further Information

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Relative Metric

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