Epigenetic Changes of CXCR4 and Its Ligand CXCL12 as Prognostic Factors for Sporadic Breast Cancer
Publication Date
December 29, 2011
Journal
PLOS ONE
Authors
Edneia A. S. Ramos, Mariana Grochoski, Karin Braun Prado, Gerusa G. Seniski, et al
Volume
6
Issue
12
Pages
e29461
DOI
https://dx.plos.org/10.1371/journal.pone.0029461
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0029461
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22220212
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248418
Europe PMC
http://europepmc.org/abstract/MED/22220212
Web of Science
000300677000036
Scopus
84855272662
Mendeley
http://www.mendeley.com/research/epigenetic-changes-cxcr4-ligand-cxcl12-prognostic-factors-sporadic-breast-cancer
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Mendeley | Further Information

{"title"=>"Epigenetic changes of CXCR4 and its ligand CXCL12 as prognostic factors for sporadic breast cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Edneia A.S.", "last_name"=>"Ramos", "scopus_author_id"=>"26427777600"}, {"first_name"=>"Mariana", "last_name"=>"Grochoski", "scopus_author_id"=>"26427635000"}, {"first_name"=>"Karin", "last_name"=>"Braun-Prado", "scopus_author_id"=>"24074049600"}, {"first_name"=>"Gerusa G.", "last_name"=>"Seniski", "scopus_author_id"=>"26427849300"}, {"first_name"=>"Iglenir J.", "last_name"=>"Cavalli", "scopus_author_id"=>"6701487354"}, {"first_name"=>"Enilze M.S.F.", "last_name"=>"Ribeiro", "scopus_author_id"=>"55438762700"}, {"first_name"=>"Anamaria A.", "last_name"=>"Camargo", "scopus_author_id"=>"7005065206"}, {"first_name"=>"Fabrício F.", "last_name"=>"Costa", "scopus_author_id"=>"15519007800"}, {"first_name"=>"Giseli", "last_name"=>"Klassen", "scopus_author_id"=>"7005895864"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84855272662", "pui"=>"364024665", "doi"=>"10.1371/journal.pone.0029461", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84855272662", "pmid"=>"22220212"}, "id"=>"19f4e7ae-484f-3c6a-8b3e-1c7e1c37fd90", "abstract"=>"Chemokines and their receptors are involved in the development and cancer progression. The chemokine CXCL12 interacts with its receptor, CXCR4, to promote cellular adhesion, survival, proliferation and migration. The CXCR4 gene is upregulated in several types of cancers, including skin, lung, pancreas, brain and breast tumors. In pancreatic cancer and melanoma, CXCR4 expression is regulated by DNA methylation within its promoter region. In this study we examined the role of cytosine methylation in the regulation of CXCR4 expression in breast cancer cell lines and also correlated the methylation pattern with the clinicopathological aspects of sixty-nine primary breast tumors from a cohort of Brazilian women. RT-PCR showed that the PMC-42, MCF7 and MDA-MB-436 breast tumor cell lines expressed high levels of CXCR4. Conversely, the MDA-MB-435 cell line only expressed CXCR4 after treatment with 5-Aza-CdR, which suggests that CXCR4 expression is regulated by DNA methylation. To confirm this hypothesis, a 184 bp fragment of the CXCR4 gene promoter region was cloned after sodium bisulfite DNA treatment. Sequencing data showed that cell lines that expressed CXCR4 had only 15% of methylated CpG dinucleotides, while the cell line that not have CXCR4 expression, had a high density of methylation (91%). Loss of DNA methylation in the CXCR4 promoter was detected in 67% of the breast cancer analyzed. The absence of CXCR4 methylation was associated with the tumor stage, size, histological grade, lymph node status, ESR1 methylation and CXCL12 methylation, metastasis and patient death. Kaplan-Meier curves demonstrated that patients with an unmethylated CXCR4 promoter had a poorer overall survival and disease-free survival. Furthermore, patients with both CXCL12 methylation and unmethylated CXCR4 had a shorter overall survival and disease-free survival. These findings suggest that the DNA methylation status of both CXCR4 and CXCL12 genes could be used as a biomarker for prognosis in breast cancer.", "link"=>"http://www.mendeley.com/research/epigenetic-changes-cxcr4-ligand-cxcl12-prognostic-factors-sporadic-breast-cancer", "reader_count"=>56, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Student > Doctoral Student"=>3, "Researcher"=>13, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>3, "Student > Master"=>8, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Student > Doctoral Student"=>3, "Researcher"=>13, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>3, "Student > Master"=>8, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>12, "Agricultural and Biological Sciences"=>27, "Arts and Humanities"=>1, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Belgium"=>1, "Uruguay"=>2, "United States"=>2, "Brazil"=>1, "United Kingdom"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/697618"], "description"=>"<p><i>CXCR4</i> methylation status and the correlation with (A) overall survival (OS) and (B) disease-free survival (DFS) are shown. <i>CXCL12</i> methylation status and association to <i>CXCR4</i> methylation for (C) OS and (D) DFS are shown.</p>", "links"=>[], "tags"=>["meier", "curves", "disease-free", "methylation"], "article_id"=>368006, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Edneia A. S. Ramos", "Mariana Grochoski", "Karin Braun-Prado", "Gerusa G. Seniski", "Iglenir J. Cavalli", "Enilze M. S. F. Ribeiro", "Anamaria A. Camargo", "Fabricio F. Costa", "Giseli Klassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029461.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curves_for_overall_survival_and_disease_free_survival_according_to_the_methylation_status_of_CXCR4_and_CXCL12_/368006", "title"=>"Kaplan Meier curves for overall survival and disease-free survival according to the methylation status of <i>CXCR4</i> and <i>CXCL12</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:22:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/697482"], "description"=>"<p>(A) Primer standardization for methylated and unmethylated conditions in tumor cell lines. (B) MSP analysis of primary tumors. Thirteen samples are represented. MW, Molecular Weight; NC, Negative Control.</p>", "links"=>[], "tags"=>["cancer", "lines"], "article_id"=>367874, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Edneia A. S. Ramos", "Mariana Grochoski", "Karin Braun-Prado", "Gerusa G. Seniski", "Iglenir J. Cavalli", "Enilze M. S. F. Ribeiro", "Anamaria A. Camargo", "Fabricio F. Costa", "Giseli Klassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029461.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MSP_analysis_in_breast_cancer_cell_lines_and_primary_breast_tumors_/367874", "title"=>"MSP analysis in breast cancer cell lines and primary breast tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:21:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/697396"], "description"=>"<p>The cell lines used are shown. The nineteen dinucleotides are numbered in agreement with the sequence. The open circles represent the unmethylated dinucleotides while the gray to black portion represents the percentage of methylation. On the right side methylation pattern are represented according to data of RT-PCR and the absolute percentage value. The arrows below the CpG dinucleotides represent the MSP primers that were used.</p>", "links"=>[], "tags"=>["sequencing", "promoter", "cancer"], "article_id"=>367787, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Edneia A. S. Ramos", "Mariana Grochoski", "Karin Braun-Prado", "Gerusa G. Seniski", "Iglenir J. Cavalli", "Enilze M. S. F. Ribeiro", "Anamaria A. Camargo", "Fabricio F. Costa", "Giseli Klassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029461.g002", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bisulfite_sequencing_of_the_CXCR4_gene_promoter_in_the_breast_cancer_cell_lines_/367787", "title"=>"Bisulfite sequencing of the <i>CXCR4</i> gene promoter in the breast cancer cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:20:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/697835"], "description"=>"<p><b>Abbreviations:</b><i>p</i>, value from statistical analysis <i>χ<sup>2</sup></i> test and Fisher's exact test; M, methylated; U unmethylated; significant data are in bold.</p><p>*<i>CXCL12</i> and <i>ESR1</i> methylation data were used from a previous study published by our group <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029461#pone.0029461-Ramos1\" target=\"_blank\">[17]</a>.</p>", "links"=>[], "tags"=>["69", "patients", "carcinomas", "methylation"], "article_id"=>368220, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Edneia A. S. Ramos", "Mariana Grochoski", "Karin Braun-Prado", "Gerusa G. Seniski", "Iglenir J. Cavalli", "Enilze M. S. F. Ribeiro", "Anamaria A. Camargo", "Fabricio F. Costa", "Giseli Klassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029461.t001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinicopathological_features_of_69_patients_with_primary_breast_carcinomas_and_methylation_status_of_CXCR4_gene_/368220", "title"=>"Clinicopathological features of 69 patients with primary breast carcinomas and methylation status of <i>CXCR4</i> gene.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 10:23:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/697298"], "description"=>"<p>(A) The bands represent <i>CXCR4</i> expression in the PMC-42, MCF7, MDA-MB-436 cell lines and (B) MDA-MB-435 mock or MDA-MB-435 D-Aza represent the MDA-MB-435 cell line before and after treatment with 5-aza-2′-deoxycytidine, respectively. The <i>GAPDH</i> gene was used as a positive control in both experiments. MW, Molecular Weight, NC represents the PCR reaction without DNA (negative control).</p>", "links"=>[], "tags"=>["semi-quantitative", "rt-pcr", "cancer", "lines"], "article_id"=>367676, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Edneia A. S. Ramos", "Mariana Grochoski", "Karin Braun-Prado", "Gerusa G. Seniski", "Iglenir J. Cavalli", "Enilze M. S. F. Ribeiro", "Anamaria A. Camargo", "Fabricio F. Costa", "Giseli Klassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029461.g001", "stats"=>{"downloads"=>3, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CXCR4_expression_analysis_using_semi_quantitative_RT_PCR_in_breast_cancer_tumor_cell_lines_and_CXCR4_expression_after_5_aza_2_deoxycytidine_D_Aza_treatment_/367676", "title"=>"<i>CXCR4</i> expression analysis using semi-quantitative RT-PCR in breast cancer tumor cell lines and <i>CXCR4</i> expression after 5-aza-2′-deoxycytidine (D-Aza) treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:20:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/697786"], "description"=>"<p><b>Abbreviations:</b> M, specific for methylated condition; U, specific for unmethylated condition.</p>", "links"=>[], "tags"=>["primers", "nested-pcr"], "article_id"=>368179, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Edneia A. S. Ramos", "Mariana Grochoski", "Karin Braun-Prado", "Gerusa G. Seniski", "Iglenir J. Cavalli", "Enilze M. S. F. Ribeiro", "Anamaria A. Camargo", "Fabricio F. Costa", "Giseli Klassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029461.t002", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sequence_of_the_primers_used_for_RT_PCR_nested_PCR_and_MSP_/368179", "title"=>"Sequence of the primers used for RT-PCR, nested-PCR and MSP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 10:22:50"}

PMC Usage Stats | Further Information

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Relative Metric

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