A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma
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{"title"=>"A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma", "type"=>"journal", "authors"=>[{"first_name"=>"Jeran K.", "last_name"=>"Stratford", "scopus_author_id"=>"26654540600"}, {"first_name"=>"David J.", "last_name"=>"Bentrem", "scopus_author_id"=>"6603741820"}, {"first_name"=>"Judy M.", "last_name"=>"Anderson", "scopus_author_id"=>"15922202200"}, {"first_name"=>"Cheng", "last_name"=>"Fan", "scopus_author_id"=>"12808634800"}, {"first_name"=>"Keith A.", "last_name"=>"Volmar", "scopus_author_id"=>"36438863200"}, {"first_name"=>"J. S.", "last_name"=>"Marron", "scopus_author_id"=>"35411635500"}, {"first_name"=>"Elizabeth D.", "last_name"=>"Routh", "scopus_author_id"=>"26641311200"}, {"first_name"=>"Laura S.", "last_name"=>"Caskey", "scopus_author_id"=>"6602453708"}, {"first_name"=>"Jonathan C.", "last_name"=>"Samuel", "scopus_author_id"=>"14323840800"}, {"first_name"=>"Channing J.", "last_name"=>"Der", "scopus_author_id"=>"35597766000"}, {"first_name"=>"Leigh B.", "last_name"=>"Thorne", "scopus_author_id"=>"55371176100"}, {"first_name"=>"Benjamin F.", "last_name"=>"Calvo", "scopus_author_id"=>"35596684400"}, {"first_name"=>"Hong Jin", "last_name"=>"Kim", "scopus_author_id"=>"35086299200"}, {"first_name"=>"Mark S.", "last_name"=>"Talamonti", "scopus_author_id"=>"35427881200"}, {"first_name"=>"Christine A.", "last_name"=>"Iacobuzio-Donahue", "scopus_author_id"=>"7003847868"}, {"first_name"=>"Michael A.", "last_name"=>"Hollingsworth", "scopus_author_id"=>"7102604437"}, {"first_name"=>"Charles M.", "last_name"=>"Perou", "scopus_author_id"=>"7003834979"}, {"first_name"=>"Jen Jen", "last_name"=>"Yeh", "scopus_author_id"=>"9278061900"}], "year"=>2010, "source"=>"PLoS Medicine", "identifiers"=>{"scopus"=>"2-s2.0-77955048480", "doi"=>"10.1371/journal.pmed.1000307", "sgr"=>"77955048480", "isbn"=>"1549-1676", "pmid"=>"20644708", "issn"=>"15491277", "pui"=>"359258174"}, "id"=>"7fa7f4e2-2e88-3348-9179-683e5c2bdd24", "abstract"=>"BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.\\n\\nMETHODS AND FINDINGS: We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.\\n\\nCONCLUSIONS: Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.", "link"=>"http://www.mendeley.com/research/sixgene-signature-predicts-survival-patients-localized-pancreatic-ductal-adenocarcinoma-2", "reader_count"=>73, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>6, "Student > Doctoral Student"=>4, "Researcher"=>27, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>5, "Other"=>2, "Student > Master"=>3, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>6, "Student > Doctoral Student"=>4, "Researcher"=>27, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>5, "Other"=>2, "Student > Master"=>3, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>5, "Mathematics"=>2, "Agricultural and Biological Sciences"=>31, "Medicine and Dentistry"=>20, "Neuroscience"=>1, "Sports and Recreations"=>1, "Social Sciences"=>2, "Computer Science"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>20}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>31}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"United States"=>4, "China"=>1, "Australia"=>1, "Germany"=>2, "Spain"=>1}, "group_count"=>6}

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  • {"files"=>["https://ndownloader.figshare.com/files/418657", "https://ndownloader.figshare.com/files/418687"], "description"=>"<div><h3>Background</h3><p>Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.</p><h3>Methods and Findings</h3><p>We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7–10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.</p><h3>Conclusions</h3><p>Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets.</p><h3></h3><p><em>Please see later in the article for the Editors' Summary</em></p></div>", "links"=>[], "tags"=>["six-gene", "patients", "localized", "pancreatic", "ductal", "adenocarcinoma"], "article_id"=>142673, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.s001", "https://dx.doi.org/10.1371/journal.pmed.1000307.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Six_Gene_Signature_Predicts_Survival_of_Patients_with_Localized_Pancreatic_Ductal_Adenocarcinoma/142673", "title"=>"A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-07-13 00:44:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/840759"], "description"=>"<p>Clustering of (A) the six genes defined by SAM evaluation of the metastatic compared to nonmetastatic primary PDAC using a false discovery rate of 5%; (B) patient samples into high- and low-risk groups in a training set of 34 patients with localized and resected PDAC using the X-tile determined cut-point of a Pearson correlation coefficient of zero; (C) patient samples into high- and low-risk groups in an independent test set of 67 patients with localized and resected PDAC using the predetermined cut-point of zero. Kaplan-Meier overall survival of (D) the training set classified into high- and low-risk groups according to the X-tile determined cut-point of a Pearson correlation coefficient of zero; (E) and the independent test set classified into high- and low-risk groups according to the same predetermined cut-point.</p>", "links"=>[], "tags"=>["six-gene"], "article_id"=>511201, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_development_and_application_of_a_six_gene_signature_for_PDAC_/511201", "title"=>"Identification, development, and application of a six-gene signature for PDAC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-13 00:20:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/840911"], "description"=>"<p>(A) KLF6 staining is significantly higher in PDAC compared to normal adjacent pancreas in an independent dataset of a 50-patient TMA (UNC2) as well as NEB samples used for the original analysis. (B) Kaplan-Meier overall survival of 50 patients classified by high and low KLF6 scores, using the median cutoff score of 1.5. (C) KLF6 immunostaining in the primary tumor of a patient who died of metastatic disease (ii) and in a resected primary tumor (iv). Minimal staining is seen in the matched normal adjacent tissue of both patients (i, iii). KLF6 immunostaining in islet cells (i, white arrowhead). Arrows illustrate normal ductal epithelium. Black arrowheads illustrate tumor.</p>", "links"=>[], "tags"=>["klf6", "fos"], "article_id"=>511344, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Significance_of_KLF6_and_Fos_B_expression_in_primary_PDAC_/511344", "title"=>"Significance of KLF6 and Fos B expression in primary PDAC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-13 00:22:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/841063"], "description"=>"<p>NA, not available.</p>", "links"=>[], "tags"=>["characteristics", "derivation"], "article_id"=>511497, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_tumor_and_treatment_characteristics_in_the_derivation_set_/511497", "title"=>"Patient, tumor, and treatment characteristics in the derivation set.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-07-13 00:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/841117"], "description"=>"<p>CI, confidence interval.</p>", "links"=>[], "tags"=>["proportional", "hazards", "regression", "six-gene"], "article_id"=>511549, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cox_proportional_hazards_regression_analysis_of_the_six_gene_signature_/511549", "title"=>"Cox proportional hazards regression analysis of the six-gene signature.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-07-13 00:25:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/841175"], "description"=>"<p>NA, not available.</p>", "links"=>[], "tags"=>["characteristics"], "article_id"=>511609, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_tumor_and_treatment_characteristics_in_the_training_and_testing_sets_/511609", "title"=>"Patient, tumor, and treatment characteristics in the training and testing sets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-07-13 00:26:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/841230"], "description"=>"<p>Relationship between the six-gene signature and clinicopathological variables.</p>", "links"=>[], "tags"=>["six-gene", "clinicopathological"], "article_id"=>511666, "categories"=>["Cancer", "Genetics"], "users"=>["Jeran K. Stratford", "David J. Bentrem", "Judy M. Anderson", "Cheng Fan", "Keith A. Volmar", "J. S. Marron", "Elizabeth D. Routh", "Laura S. Caskey", "Jonathan C. Samuel", "Channing J. Der", "Leigh B. Thorne", "Benjamin F. Calvo", "Hong Jin Kim", "Mark S. Talamonti", "Christine A. Iacobuzio-Donahue", "Michael A. Hollingsworth", "Charles M. Perou", "Jen Jen Yeh"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000307.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relationship_between_the_six_gene_signature_and_clinicopathological_variables_/511666", "title"=>"Relationship between the six-gene signature and clinicopathological variables.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-07-13 00:27:46"}

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