Epidermal Growth Factor Receptor Tyrosine Kinase Defines Critical Prognostic Genes of Stage I Lung Adenocarcinoma
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{"title"=>"Epidermal Growth Factor Receptor Tyrosine Kinase Defines Critical Prognostic Genes of Stage I Lung Adenocarcinoma", "type"=>"journal", "authors"=>[{"first_name"=>"Mai", "last_name"=>"Yamauchi", "scopus_author_id"=>"56783635600"}, {"first_name"=>"Rui", "last_name"=>"Yamaguchi", "scopus_author_id"=>"8868542400"}, {"first_name"=>"Asuka", "last_name"=>"Nakata", "scopus_author_id"=>"55314994800"}, {"first_name"=>"Takashi", "last_name"=>"Kohno", "scopus_author_id"=>"7201820330"}, {"first_name"=>"Masao", "last_name"=>"Nagasaki", "scopus_author_id"=>"7005461981"}, {"first_name"=>"Teppei", "last_name"=>"Shimamura", "scopus_author_id"=>"24462844900"}, {"first_name"=>"Seiya", "last_name"=>"Imoto", "scopus_author_id"=>"7102856656"}, {"first_name"=>"Ayumu", "last_name"=>"Saito", "scopus_author_id"=>"15847012800"}, {"first_name"=>"Kazuko", "last_name"=>"Ueno", "scopus_author_id"=>"16481361600"}, {"first_name"=>"Yousuke", "last_name"=>"Hatanaka", "scopus_author_id"=>"55364030000"}, {"first_name"=>"Ryo", "last_name"=>"Yoshida", "scopus_author_id"=>"35239118600"}, {"first_name"=>"Tomoyuki", "last_name"=>"Higuchi", "scopus_author_id"=>"8093528900"}, {"first_name"=>"Masaharu", "last_name"=>"Nomura", "scopus_author_id"=>"35308853800"}, {"first_name"=>"David G.", "last_name"=>"Beer", "scopus_author_id"=>"7103198346"}, {"first_name"=>"Jun", "last_name"=>"Yokota", "scopus_author_id"=>"7102553031"}, {"first_name"=>"Satoru", "last_name"=>"Miyano", "scopus_author_id"=>"7102554029"}, {"first_name"=>"Noriko", "last_name"=>"Gotoh", "scopus_author_id"=>"7006670309"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84866529515", "pmid"=>"23028479", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"365690664", "issn"=>"19326203", "scopus"=>"2-s2.0-84866529515", "doi"=>"10.1371/journal.pone.0043923"}, "id"=>"29f55e6a-6981-3d79-9288-eeef7165e4fd", "abstract"=>"PURPOSE: To identify stage I lung adenocarcinoma patients with a poor prognosis who will benefit from adjuvant therapy.\\n\\nPATIENTS AND METHODS: Whole gene expression profiles were obtained at 19 time points over a 48-hour time course from human primary lung epithelial cells that were stimulated with epidermal growth factor (EGF) in the presence or absence of a clinically used EGF receptor tyrosine kinase (RTK)-specific inhibitor, gefitinib. The data were subjected to a mathematical simulation using the State Space Model (SSM). \"Gefitinib-sensitive\" genes, the expressional dynamics of which were altered by addition of gefitinib, were identified. A risk scoring model was constructed to classify high- or low-risk patients based on expression signatures of 139 gefitinib-sensitive genes in lung cancer using a training data set of 253 lung adenocarcinomas of North American cohort. The predictive ability of the risk scoring model was examined in independent cohorts of surgical specimens of lung cancer.\\n\\nRESULTS: The risk scoring model enabled the identification of high-risk stage IA and IB cases in another North American cohort for overall survival (OS) with a hazard ratio (HR) of 7.16 (P = 0.029) and 3.26 (P = 0.0072), respectively. It also enabled the identification of high-risk stage I cases without bronchioalveolar carcinoma (BAC) histology in a Japanese cohort for OS and recurrence-free survival (RFS) with HRs of 8.79 (P = 0.001) and 3.72 (P = 0.0049), respectively.\\n\\nCONCLUSION: The set of 139 gefitinib-sensitive genes includes many genes known to be involved in biological aspects of cancer phenotypes, but not known to be involved in EGF signaling. The present result strongly re-emphasizes that EGF signaling status in cancer cells underlies an aggressive phenotype of cancer cells, which is useful for the selection of early-stage lung adenocarcinoma patients with a poor prognosis.\\n\\nTRIAL REGISTRATION: The Gene Expression Omnibus (GEO) GSE31210.", "link"=>"http://www.mendeley.com/research/epidermal-growth-factor-receptor-tyrosine-kinase-defines-critical-prognostic-genes-stage-i-lung-aden-4", "reader_count"=>14, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>5, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Japan"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/574048"], "description"=>"<p>HR, hazard ratio; CI, confidence interval.</p>", "links"=>[], "tags"=>["ratios"], "article_id"=>244518, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.t002", "stats"=>{"downloads"=>5, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hazard_ratios_for_overall_survival_OS_/244518", "title"=>"Hazard ratios for overall survival (OS).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-19 01:15:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/573340"], "description"=>"<p>(A) A diagram of the <i>in vivo</i> experimental procedures. The serum-starved cells were stimulated with EGF (100 ng/mL) in the presence or absence of gefitinib (0.5 μM) for 48 h at 37°C. Before stimulation with EGF, cells were starved for 24 h at 37°C. Total RNA was isolated at each time point as indicated by the arrows (19 time points); the same experiments were performed two or three times at several time points. (B) Schematic view of time-course gene expression patterns of predicted or observed gene expression levels. The blue solid line represents a predicted gene expression pattern based on the EGF-response SSM, using the observed gene expression levels derived from the EGF-treated cells (x). (C) The red solid line represents a predicted gene expression pattern based on the EGF-response SSM, using the observed gene expression levels derived from the EGF+gefitinib-treated cells (o). (D, E) A representative gene expression pattern of gefitinib-sensitive genes (D) and -insensitive genes (E). Left panels: observed gene expression patterns in EGF-treated cells (x in blue) and EGF-response SSM-predicted gene expression patterns (blue dotted line). Right panels: observed gene expression patterns in EGF+gefitinib-treated cells (o in red) and the EGF-response SSM-predicted gene expression patterns (red solid line).</p>", "links"=>[], "tags"=>["procedures", "ssm"], "article_id"=>243811, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Diagrams_of_experimental_procedures_and_gene_set_selection_by_SSM_analysis_/243811", "title"=>"Diagrams of experimental procedures and gene set selection by SSM analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-19 01:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/573728"], "description"=>"<p>Kaplan-Meier plot survival estimates are depicted for high- (red line) and low- (black line) risk groups by analyzing the NCI validation data sets containing two data sets designated as MSK and CAN/DF (A), and the Duke data set (B). P-values were obtained with the use of the log-rank test. Numbers in parentheses represent the number of patients that were segregated.</p>", "links"=>[], "tags"=>["nci", "validation", "sets", "duke", "139"], "article_id"=>244189, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_power_of_survival_prediction_for_the_NCI_validation_data_sets_and_the_Duke_data_set_using_the_139_genes_/244189", "title"=>"The power of survival prediction for the NCI validation data sets and the Duke data set using the 139 genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-19 01:09:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/305218", "https://ndownloader.figshare.com/files/305352", "https://ndownloader.figshare.com/files/305480", "https://ndownloader.figshare.com/files/305653", "https://ndownloader.figshare.com/files/305800", "https://ndownloader.figshare.com/files/305972", "https://ndownloader.figshare.com/files/306102", "https://ndownloader.figshare.com/files/306123", "https://ndownloader.figshare.com/files/306136", "https://ndownloader.figshare.com/files/306154", "https://ndownloader.figshare.com/files/306169", "https://ndownloader.figshare.com/files/306198", "https://ndownloader.figshare.com/files/306219", "https://ndownloader.figshare.com/files/306238"], "description"=>"<div><h3>Purpose</h3><p>To identify stage I lung adenocarcinoma patients with a poor prognosis who will benefit from adjuvant therapy.</p> <h3>Patients and Methods</h3><p>Whole gene expression profiles were obtained at 19 time points over a 48-hour time course from human primary lung epithelial cells that were stimulated with epidermal growth factor (EGF) in the presence or absence of a clinically used EGF receptor tyrosine kinase (RTK)-specific inhibitor, gefitinib. The data were subjected to a mathematical simulation using the State Space Model (SSM). “Gefitinib-sensitive” genes, the expressional dynamics of which were altered by addition of gefitinib, were identified. A risk scoring model was constructed to classify high- or low-risk patients based on expression signatures of 139 gefitinib-sensitive genes in lung cancer using a training data set of 253 lung adenocarcinomas of North American cohort. The predictive ability of the risk scoring model was examined in independent cohorts of surgical specimens of lung cancer.</p> <h3>Results</h3><p>The risk scoring model enabled the identification of high-risk stage IA and IB cases in another North American cohort for overall survival (OS) with a hazard ratio (HR) of 7.16 (P = 0.029) <u>and</u> 3.26 (P = 0.0072), respectively. It also enabled the identification of high-risk stage I cases without bronchioalveolar carcinoma (BAC) histology in a Japanese cohort for OS and recurrence-free survival (RFS) with HRs of 8.79 (P = 0.001) and 3.72 (P = 0.0049), respectively.</p> <h3>Conclusion</h3><p>The set of 139 gefitinib-sensitive genes includes many genes known to be involved in biological aspects of cancer phenotypes, but not known to be involved in EGF signaling. The present result strongly re-emphasizes that EGF signaling status in cancer cells underlies an aggressive phenotype of cancer cells, which is useful for the selection of early-stage lung adenocarcinoma patients with a poor prognosis.</p> <h3>Trial Registration</h3><p>The Gene Expression Omnibus (GEO) <a href=\"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31210+\">GSE31210</a></p> </div>", "links"=>[], "tags"=>["epidermal", "receptor", "tyrosine", "kinase", "defines", "prognostic", "genes", "adenocarcinoma"], "article_id"=>120206, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0043923.s001", "https://dx.doi.org/10.1371/journal.pone.0043923.s002", "https://dx.doi.org/10.1371/journal.pone.0043923.s003", "https://dx.doi.org/10.1371/journal.pone.0043923.s004", "https://dx.doi.org/10.1371/journal.pone.0043923.s005", "https://dx.doi.org/10.1371/journal.pone.0043923.s006", "https://dx.doi.org/10.1371/journal.pone.0043923.s007", "https://dx.doi.org/10.1371/journal.pone.0043923.s008", "https://dx.doi.org/10.1371/journal.pone.0043923.s009", "https://dx.doi.org/10.1371/journal.pone.0043923.s010", "https://dx.doi.org/10.1371/journal.pone.0043923.s011", "https://dx.doi.org/10.1371/journal.pone.0043923.s012", "https://dx.doi.org/10.1371/journal.pone.0043923.s013", "https://dx.doi.org/10.1371/journal.pone.0043923.s014"], "stats"=>{"downloads"=>59, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Epidermal_Growth_Factor_Receptor_Tyrosine_Kinase_Defines_Critical_Prognostic_Genes_of_Stage_I_Lung_Adenocarcinoma/120206", "title"=>"Epidermal Growth Factor Receptor Tyrosine Kinase Defines Critical Prognostic Genes of Stage I Lung Adenocarcinoma", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-19 00:03:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/573939"], "description"=>"*<p>Representative pathways derived from the IPA analysis are listed.</p>", "links"=>[], "tags"=>["cross-talk", "pathways", "encoded", "139"], "article_id"=>244408, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.t004", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Potential_cross_talk_among_pathways_encoded_by_the_139_genes_/244408", "title"=>"Potential cross-talk among pathways encoded by the 139 genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-19 01:13:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/573858"], "description"=>"<p>(A) Kaplan-Meier plots of overall survival (OS) and recurrence-free survival (RFS) estimates for the stage I NCC-Tokyo data set without BAC histology. (B) Kaplan-Meier plot OS estimates for stage I patients in the NCC-Tokyo data set divided into EGFR mutation (+) or (−) group.</p>", "links"=>[], "tags"=>["ncc-tokyo", "validation", "sets", "139"], "article_id"=>244325, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.g004", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_power_of_survival_prediction_for_NCC_Tokyo_validation_data_sets_using_the_139_genes_/244325", "title"=>"The power of survival prediction for NCC-Tokyo validation data sets using the 139 genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-19 01:12:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/573563"], "description"=>"<p>Validation procedures of the final risk scoring model using the 139 genes.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "biotechnology", "Computational biology", "oncology"], "article_id"=>244033, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_procedures_/244033", "title"=>"Validation procedures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-19 01:07:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/573985"], "description"=>"<p>HR, hazard ratio; CI, confidence interval.</p>", "links"=>[], "tags"=>["ratios", "relapse-free"], "article_id"=>244466, "categories"=>["Biological Sciences", "Molecular Biology", "Biotechnology", "Cancer", "Genetics"], "users"=>["Mai Yamauchi", "Rui Yamaguchi", "Asuka Nakata", "Takashi Kohno", "Masao Nagasaki", "Teppei Shimamura", "Seiya Imoto", "Ayumu Saito", "Kazuko Ueno", "Yousuke Hatanaka", "Ryo Yoshida", "Tomoyuki Higuchi", "Masaharu Nomura", "David G. Beer", "Jun Yokota", "Satoru Miyano", "Noriko Gotoh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043923.t003", "stats"=>{"downloads"=>1, "page_views"=>43, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hazard_ratios_for_relapse_free_survival_RFS_/244466", "title"=>"Hazard ratios for relapse-free survival (RFS).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-19 01:14:26"}

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Relative Metric

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