Induction of Wnt-Inducible Signaling Protein-1 Correlates with Invasive Breast Cancer Oncogenesis and Reduced Type 1 Cell-Mediated Cytotoxic Immunity: A Retrospective Study
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{"title"=>"Induction of Wnt-Inducible Signaling Protein-1 Correlates with Invasive Breast Cancer Oncogenesis and Reduced Type 1 Cell-Mediated Cytotoxic Immunity: A Retrospective Study", "type"=>"journal", "authors"=>[{"first_name"=>"David J.", "last_name"=>"Klinke", "scopus_author_id"=>"13102554800"}], "year"=>2014, "source"=>"PLoS Computational Biology", "identifiers"=>{"isbn"=>"1553-7358 (Electronic)\\r1553-734X (Linking)", "pmid"=>"24426833", "doi"=>"10.1371/journal.pcbi.1003409", "pui"=>"372348789", "issn"=>"1553734X", "sgr"=>"84896707403", "scopus"=>"2-s2.0-84896707403"}, "id"=>"fc0e05fa-6350-3980-85a2-f702c6e39aea", "abstract"=>"Innate and type 1 cell-mediated cytotoxic immunity function as important extracellular control mechanisms that maintain cellular homeostasis. Interleukin-12 (IL12) is an important cytokine that links innate immunity with type 1 cell-mediated cytotoxic immunity. We recently observed in vitro that tumor-derived Wnt-inducible signaling protein-1 (WISP1) exerts paracrine action to suppress IL12 signaling. The objective of this retrospective study was three fold: 1) to determine whether a gene signature associated with type 1 cell-mediated cytotoxic immunity was correlated with overall survival, 2) to determine whether WISP1 expression is increased in invasive breast cancer, and 3) to determine whether a gene signature consistent with inhibition of IL12 signaling correlates with WISP1 expression. Clinical information and mRNA expression for genes associated with anti-tumor immunity were obtained from the invasive breast cancer arm of the Cancer Genome Atlas study. Patient cohorts were identified using hierarchical clustering. The immune signatures associated with the patient cohorts were interpreted using model-based inference of immune polarization. Reverse phase protein array, tissue microarray, and quantitative flow cytometry in breast cancer cell lines were used to validate observed differences in gene expression. We found that type 1 cell-mediated cytotoxic immunity was correlated with increased survival in patients with invasive breast cancer, especially in patients with invasive triple negative breast cancer. Oncogenic transformation in invasive breast cancer was associated with an increase in WISP1. The gene expression signature in invasive breast cancer was consistent with WISP1 as a paracrine inhibitor of type 1 cell-mediated immunity through inhibiting IL12 signaling and promoting type 2 immunity. Moreover, model-based inference helped identify appropriate immune signatures that can be used as design constraints in genetically engineering better pre-clinical models of breast cancer.", "link"=>"http://www.mendeley.com/research/induction-wntinducible-signaling-protein1-correlates-invasive-breast-cancer-oncogenesis-reduced-type", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>3, "Neuroscience"=>1, "Chemistry"=>1, "Psychology"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1343441"], "description"=>"<p>Adjuvant treatment of breast cancer is stratified based upon the molecular histology, as summarized by a Venn diagram for this cohort (A). While treatments were documented for 224 of the 520 patients in the cohort, the distribution of known adjuvant therapies are indicated by the color circles (Hormone therapy - blue circle, chemotherapy - green circle, and Herceptin immunotherapy - red circle). Kaplan-Meier survival curves were obtained for invasive breast cancer patients that were stratified by group membership (group 1 - blue curves, group 2 - red curves) within a common adjuvant treatment group. The treatment groups included triple negative breast cancer (B), patients treated with adjuvant Herceptin plus HER2+ patients with unknown treatment (C), and patients treated with adjuvant hormone therapy plus other HER2- patients (D). Dotted lines indicate 95% confidence bounds. The number of patients at risk as a function of time are shown below the x-axis for each Kaplan-Meier curve. A p–value of less than 0.05 was considered statistically significant.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "cancer", "patients", "enhanced", "type-1", "cell-mediated", "immunity", "6-year"], "article_id"=>898080, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Triple_negative_breast_cancer_patients_with_enhanced_type_1_cell_mediated_immunity_exhibit_an_improved_6_year_survival_/898080", "title"=>"Triple negative breast cancer patients with enhanced type-1 cell-mediated immunity exhibit an improved 6-year survival.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343454"], "description"=>"<p>Statistical significance between group summary statistics was estimated using a two-sided unmatched Student's t test († indicates p–value = 0.48). A Fisher's Exact test was used to test whether categorical data for group is different than population (‡ indicates p–value greater than 0.5, * indicates p–value less than 1x10<sup>-4</sup>). Age summarized as mean and range that encloses 95% of the population. Odds ratio calculated based upon diagnosis of TN breast cancer within each cohort group.</p><p>LN = Lymph node.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "stratified"], "article_id"=>898089, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_the_patient_population_stratified_by_group_membership_/898089", "title"=>"Characteristics of the patient population stratified by group membership.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343451"], "description"=>"<p>(A) Relative immune cell infiltrate was estimated based upon the average expression of genes associated with NK cells (KLRD1, KLRC2, KLRC3), T cells (CD247, CD3G, CD3D, CD3E), and macrophages (CD14, CPM, MRC1, ITGAM) in the breast cancer GEMM data set <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi.1003409-Herschkowitz1\" target=\"_blank\">[46]</a>. (B) Using model-based inference, the mean posterior probabilities associated with T helper cell and macrophage polarization in each GEMM group were estimated based upon mutually exclusive gene expression patterns that are associated with each cell polarization subset, as listed in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi-1003409-t001\" target=\"_blank\">Table 1</a>. The immune polarization signature was compared to a signature assembled from a bootstrapped ensemble of random sets of gene expression (i.e., a null hypothesis), as summarized by the gray shaded density distribution. In both panels, results are colored by group indicated at the top of the GEMM heatmap shown in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi-1003409-g006\" target=\"_blank\">Figure 6</a> (Normals - black, Group 1 - red, Group 2 - blue, and Group 3 - orange). In panel A, bivariate scatter plots are shown below the diagonal, marginalized histograms stratified by the three groups are shown on the diagonal, and correlation coefficients are shown above the diagonal.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "clusters", "gemm"], "article_id"=>898088, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g007", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_clusters_of_GEMM_gene_expression_exhibit_different_immune_cell_signatures_/898088", "title"=>"Hierarchical clusters of GEMM gene expression exhibit different immune cell signatures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343447"], "description"=>"<p>mRNA expression obtained from normal and breast cancer carcinoma tissue samples derived from different genetically engineered mouse models (columns) were hierarchically clustered into four groups based upon the log2 median normalized expression ratio for genes (rows) related to cell-mediated cytotoxic immunity and tumor immunosuppression. The color-coded bar at the top of the heatmap indicates the four groups (Normals - black, Group 1 - blue, Group 2 - red, and Group 3 - orange). Gene expression is shown as a row-normalized heatmap, where red denotes under-expressed and violet denotes overexpressed relative to the population mean. Dendrogram indicates the degree of similarity among genes (rows) or samples (columns) using the Ward's minimum distance method in R.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "signatures", "genetically", "engineered", "cancer", "clusters"], "article_id"=>898086, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immune_gene_expression_signatures_in_genetically_engineered_mouse_models_for_breast_cancer_clusters_into_three_groups_/898086", "title"=>"Immune gene expression signatures in genetically engineered mouse models for breast cancer clusters into three groups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343458"], "description"=>"<p>Genes associated with type 1 cell-mediated immunity.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "cell-mediated"], "article_id"=>898090, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_associated_with_type_1_cell_mediated_immunity_/898090", "title"=>"Genes associated with type 1 cell-mediated immunity.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343446"], "description"=>"<p>Copy numbers of membrane proteins IL12RB1 (A), IL12RB2 (B) and HLA-ABC (D) were quantified using flow cytometry for four breast cell lines: 184A1 HMECs (blue), BT474 (HER2+/ER+/PR+) cells (red), SKBR3 (HER2+/ER−/PR−) cells (green), and MDA-MD-231 (HER2−/ER−/PR−) cells (black). Unstained cells are shaded in gray. Results are representative of three independent replicates. (C) The ratio of IL12RB2/IL12RB1 was increased in MDA-MB-231 cells relative to the other three cell lines (* indicates a p–value<0.05, as estimated using an unpaired two-tailed Student's t-test).</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "numbers", "mhc", "cancer", "lines", "cohort", "molecular"], "article_id"=>898085, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g005", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Basal_copy_numbers_of_IL12RB1_IL12RB2_and_MHC_class_I_in_breast_cancer_cell_lines_were_consistent_with_cohort_group_assignment_based_upon_molecular_pathology_/898085", "title"=>"Basal copy numbers of IL12RB1, IL12RB2, and MHC class I in breast cancer cell lines were consistent with cohort group assignment based upon molecular pathology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343470", "https://ndownloader.figshare.com/files/1343471", "https://ndownloader.figshare.com/files/1343472", "https://ndownloader.figshare.com/files/1343473", "https://ndownloader.figshare.com/files/1343474", "https://ndownloader.figshare.com/files/1343475", "https://ndownloader.figshare.com/files/1343476", "https://ndownloader.figshare.com/files/1343477", "https://ndownloader.figshare.com/files/1343478", "https://ndownloader.figshare.com/files/1343479"], "description"=>"<div><p>Innate and type 1 cell-mediated cytotoxic immunity function as important extracellular control mechanisms that maintain cellular homeostasis. Interleukin-12 (IL12) is an important cytokine that links innate immunity with type 1 cell-mediated cytotoxic immunity. We recently observed in vitro that tumor-derived Wnt-inducible signaling protein-1 (WISP1) exerts paracrine action to suppress IL12 signaling. The objective of this retrospective study was three fold: 1) to determine whether a gene signature associated with type 1 cell-mediated cytotoxic immunity was correlated with overall survival, 2) to determine whether WISP1 expression is increased in invasive breast cancer, and 3) to determine whether a gene signature consistent with inhibition of IL12 signaling correlates with WISP1 expression. Clinical information and mRNA expression for genes associated with anti-tumor immunity were obtained from the invasive breast cancer arm of the Cancer Genome Atlas study. Patient cohorts were identified using hierarchical clustering. The immune signatures associated with the patient cohorts were interpreted using model-based inference of immune polarization. Reverse phase protein array, tissue microarray, and quantitative flow cytometry in breast cancer cell lines were used to validate observed differences in gene expression. We found that type 1 cell-mediated cytotoxic immunity was correlated with increased survival in patients with invasive breast cancer, especially in patients with invasive triple negative breast cancer. Oncogenic transformation in invasive breast cancer was associated with an increase in WISP1. The gene expression signature in invasive breast cancer was consistent with WISP1 as a paracrine inhibitor of type 1 cell-mediated immunity through inhibiting IL12 signaling and promoting type 2 immunity. Moreover, model-based inference helped identify appropriate immune signatures that can be used as design constraints in genetically engineering better pre-clinical models of breast cancer.</p></div>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "wnt-inducible", "protein-1", "correlates", "invasive", "cancer", "oncogenesis", "reduced", "cell-mediated", "cytotoxic", "retrospective"], "article_id"=>898099, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1003409.s001", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s002", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s003", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s004", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s005", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s006", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s007", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s008", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s009", "https://dx.doi.org/10.1371/journal.pcbi.1003409.s010"], "stats"=>{"downloads"=>21, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_Wnt_Inducible_Signaling_Protein_1_Correlates_with_Invasive_Breast_Cancer_Oncogenesis_and_Reduced_Type_1_Cell_Mediated_Cytotoxic_Immunity_A_Retrospective_Study_/898099", "title"=>"Induction of Wnt-Inducible Signaling Protein-1 Correlates with Invasive Breast Cancer Oncogenesis and Reduced Type 1 Cell-Mediated Cytotoxic Immunity: A Retrospective Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343445"], "description"=>"<p>Representative deconvoluted color images derived from a breast cancer tissue microarray probed using a WISP1 antibody and imaged using 3,3′ diaminobenzidine and stained using hematoxylin for three invasive breast cancer (A - top) and three normal breast (B - bottom) tissue samples (original tissue microarray images were obtained from <a href=\"http://www.proteinatlas.org\" target=\"_blank\">www.proteinatlas.org</a><a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi.1003409-Uhlen1\" target=\"_blank\">[64]</a>). Deconvoluted intensity of WISP1 staining is shown in red while cellular structures stained using hematoxylin are shown in blue. (C) The average intensity of WISP1 staining, as determined by color deconvolution of the RGB tissue microarray images, was increased in breast carcinoma (** indicates a p–value<0.001, as estimated using an unpaired two-tailed Student's t-test). Summary statistics are shown as mean +/− SD. The number of replicates included in the analysis is indicated by n. (D) GATA3 gene expression as quantified by Affymetrix microarray correlated with GATA3 protein expression as quantified by reverse phase protein array. In panel D, a bivariate scatter plot for the 340 joint measurements is shown below the diagonal, marginalized histograms stratified by the two breast cancer groups are shown on the diagonal, and a correlation coefficient is shown above the diagonal.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "gata3", "correlate"], "article_id"=>898084, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g004", "stats"=>{"downloads"=>2, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_WISP1_and_GATA3_gene_expression_correlate_with_protein_expression_/898084", "title"=>"WISP1 and GATA3 gene expression correlate with protein expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343442"], "description"=>"<p>Relative immune cell infiltrate was estimated based upon the average expression of genes associated with NK cells, T cells, and macrophages, as listed in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi-1003409-t001\" target=\"_blank\">Table 1</a> (A). Mean posterior probability associated with T helper cell and macrophage polarization in each group (Group 1 - blue line, Group 2 - red line, Normal - black dotted line, random gene expression (null hypothesis) - gray shaded density distribution) were estimated based upon mutually exclusive gene expression patterns that are associated with each cell subset, as also listed in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi-1003409-t001\" target=\"_blank\">Table 1</a> (B). WISP1 expression was increased in breast cancer relative to normal tissue samples and WISP1 expression correlated with GATA3 expression (C). The ratio of IL12RB2 to IL12RB1 was increased in Group 2 patients relative to Group 1 patients and normal breast tissue samples (D). A 1∶1 ratio between IL12RB2 and IL12RB1 gene expression is indicated by the gray dotted line in the scatter plot. In panels A, C, and D, bivariate scatter plots are shown below the diagonal, marginalized histograms stratified by the three groups are shown on the diagonal, and correlation coefficients are shown above the diagonal. Results are colored by group (Breast Cancer Group 1: blue, Breast Cancer Group 2: red, Normal breast tissue: black).</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "clusters", "invasive", "cancer", "exhibited", "differential", "cell-mediated"], "article_id"=>898081, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g003", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_clusters_associated_with_invasive_breast_cancer_exhibited_differential_cell_mediated_immune_response_relative_to_normal_breast_tissue_/898081", "title"=>"Gene expression clusters associated with invasive breast cancer exhibited differential cell-mediated immune response relative to normal breast tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1343440"], "description"=>"<p>mRNA expression obtained from normal breast and invasive breast carcinoma tissue samples (columns) acquired as part of the Cancer Genome Atlas study <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi.1003409-Koboldt1\" target=\"_blank\">[14]</a> were hierarchically clustered into two groups based upon the log2 median-normalized expression ratio for genes (rows) related to cell-mediated cytotoxic immunity and tumor immunosuppression, as listed in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003409#pcbi-1003409-t001\" target=\"_blank\">Table 1</a>. Tissue samples were characterized by morphology (i.e., normal, ductal, lobular, or other) and molecular histology (i.e., expression of the estrogen receptor (ER+), progesterone receptor (PR+), or HER2 (HER2+)), as highlighted by the blue bars on top. Gene expression is shown as a row-normalized heatmap. Red denotes under-expressed and violet denotes over-expressed relative to the population mean. Dendrogram indicates the degree of similarity among genes (rows) or samples (columns) using the Ward's minimum distance method in R.</p>", "links"=>[], "tags"=>["Computational biology", "systems biology", "Evolutionary biology", "Forms of evolution", "microevolution", "Bioengineering", "Biomedical Engineering", "oncology", "Basic cancer research", "Immune evasion", "Cancer treatment", "immunotherapy", "patterns", "genes", "cell-mediated", "immunity", "clustered"], "article_id"=>898079, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["David J. Klinke II"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003409.g001", "stats"=>{"downloads"=>7, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_patterns_of_genes_associated_with_cell_mediated_immunity_clustered_into_two_main_groups_/898079", "title"=>"Expression patterns of genes associated with cell-mediated immunity clustered into two main groups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-09 02:51:42"}

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