Preferential Activation of the Hedgehog Pathway by Epigenetic Modulations in HPV Negative HNSCC Identified with Meta-Pathway Analysis
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{"title"=>"Preferential activation of the hedgehog pathway by epigenetic modulations in HPV negative HNSCC identified with meta-pathway analysis", "type"=>"journal", "authors"=>[{"first_name"=>"Elana J.", "last_name"=>"Fertig", "scopus_author_id"=>"15768654400"}, {"first_name"=>"Ana", "last_name"=>"Markovic", "scopus_author_id"=>"56363863500"}, {"first_name"=>"Ludmila V.", "last_name"=>"Danilova", "scopus_author_id"=>"36923408600"}, {"first_name"=>"Daria A.", "last_name"=>"Gaykalova", "scopus_author_id"=>"15047798900"}, {"first_name"=>"Leslie", "last_name"=>"Cope", "scopus_author_id"=>"36146891700"}, {"first_name"=>"Christine H.", "last_name"=>"Chung", "scopus_author_id"=>"26643200300"}, {"first_name"=>"Michael F.", "last_name"=>"Ochs", "scopus_author_id"=>"7006272363"}, {"first_name"=>"Joseph A.", "last_name"=>"Califano", "scopus_author_id"=>"35426134100"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372116658", "sgr"=>"84892405276", "issn"=>"19326203", "pmid"=>"24223768", "scopus"=>"2-s2.0-84892405276", "doi"=>"10.1371/journal.pone.0078127", "isbn"=>"1932-6203"}, "id"=>"1134f648-d099-3405-a903-b242e4f0a9cb", "abstract"=>"Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and -negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV- HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV- HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV- tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV- HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV- HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers.", "link"=>"http://www.mendeley.com/research/preferential-activation-hedgehog-pathway-epigenetic-modulations-hpv-negative-hnscc-identified-metapa", "reader_count"=>22, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>9, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Ghana"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1266881"], "description"=>"<p>Patterns identified with hierarchical clustering for sample-by-sample Pearson correlations for combined gene expression and log transformed DNA methylation data, colored by whether samples are normal (black, labeled “N”), HPV-positive (blue, labeled “+”) and HPV-negative (red, labeled “−”) samples.</p>", "links"=>[], "tags"=>["dna", "methylation", "44", "hnscc", "samples", "25", "uppp"], "article_id"=>840957, "categories"=>["Biological Sciences"], "users"=>["Elana J. Fertig", "Ana Markovic", "Ludmila V. Danilova", "Daria A. Gaykalova", "Leslie Cope", "Christine H. Chung", "Michael F. Ochs", "Joseph A. Califano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078127.g002", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clustering_combined_DNA_methylation_and_gene_expression_data_from_44_HNSCC_samples_and_25_UPPP_samples_/840957", "title"=>"Clustering combined DNA methylation and gene expression data from 44 HNSCC samples and 25 UPPP samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-04 03:07:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1266880"], "description"=>"<p>Relative activity of meta-pathways associated with (a) UPPP, (b) HNSCC, (c) HPV-positive, and (d) HPV-negative samples.</p>", "links"=>[], "tags"=>["44", "hnscc", "25", "uppp"], "article_id"=>840956, "categories"=>["Biological Sciences"], "users"=>["Elana J. Fertig", "Ana Markovic", "Ludmila V. Danilova", "Daria A. Gaykalova", "Leslie Cope", "Christine H. Chung", "Michael F. Ochs", "Joseph A. Califano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078127.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Meta_pathway_activity_identified_in_44_HNSCC_and_25_UPPP_samples_/840956", "title"=>"Meta-pathway activity identified in 44 HNSCC and 25 UPPP samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-04 03:07:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1266885"], "description"=>"<p>Clinical attributes of samples Summary of clinical features of samples in discovery, validation, and TCGA sample cohorts.</p>", "links"=>[], "tags"=>["attributes", "samples", "TCGA"], "article_id"=>840961, "categories"=>["Biological Sciences"], "users"=>["Elana J. Fertig", "Ana Markovic", "Ludmila V. Danilova", "Daria A. Gaykalova", "Leslie Cope", "Christine H. Chung", "Michael F. Ochs", "Joseph A. Califano"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0078127.t001", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_attributes_of_samples_Summary_of_clinical_features_of_samples_in_discovery_validation_and_TCGA_sample_cohorts_/840961", "title"=>"Clinical attributes of samples Summary of clinical features of samples in discovery, validation, and TCGA sample cohorts.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-04 03:07:40"}

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Relative Metric

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