Plasminogen Activator Inhibitor-2 Plays a Leading Prognostic Role among Protease Families in Non-Small Cell Lung Cancer
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{"title"=>"Plasminogen activator inhibitor-2 plays a leading prognostic role among protease families in non-small cell lung cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Chia Yi", "last_name"=>"Su", "scopus_author_id"=>"56216074300"}, {"first_name"=>"Yu Peng", "last_name"=>"Liu", "scopus_author_id"=>"8935819900"}, {"first_name"=>"Chih Jen", "last_name"=>"Yang", "scopus_author_id"=>"8961752900"}, {"first_name"=>"Yuan Feng", "last_name"=>"Lin", "scopus_author_id"=>"14825447600"}, {"first_name"=>"Jean", "last_name"=>"Chiou", "scopus_author_id"=>"36701020600"}, {"first_name"=>"Li Hsing", "last_name"=>"Chi", "scopus_author_id"=>"57072731400"}, {"first_name"=>"Jih Jong", "last_name"=>"Lee", "scopus_author_id"=>"7601473432"}, {"first_name"=>"Alex T.H.", "last_name"=>"Wu", "scopus_author_id"=>"24777511600"}, {"first_name"=>"Pei Jung", "last_name"=>"Lu", "scopus_author_id"=>"7402293355"}, {"first_name"=>"Ming Shyan", "last_name"=>"Huang", "scopus_author_id"=>"56440518700"}, {"first_name"=>"Michael", "last_name"=>"Hsiao", "scopus_author_id"=>"7101897609"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"26230665", "sgr"=>"84941960777", "doi"=>"10.1371/journal.pone.0133411", "scopus"=>"2-s2.0-84941960777", "pui"=>"606057146", "issn"=>"19326203"}, "id"=>"70b682aa-02a4-319d-a2e1-39ac607aeec3", "abstract"=>"BACKGROUND: In lung cancer, uPA, its receptor (uPAR), and the inhibitors PAI-1 and PAI-2 of the plasminogen activator family interact with MMP-2 and MMP-9 of the MMP family to promote cancer progression. However, it remains undetermined which of these markers plays the most important role and may be the most useful indicator to stratify the patients by risk.\\n\\nMETHODS: We determined the individual prognostic value of these 6 markers by analyzing a derivation cohort with 98 non-small cell lung cancer patients by immunohistochemical staining. The correlation between the IHC expression levels of these markers and disease prognosis was investigated, and an immunohistochemical panel for prognostic prediction was subsequently generated through prognostic model analysis. The value of the immunohistochemical panel was then verified by a validation cohort with 91 lung cancer patients.\\n\\nRESULTS: In derivation cohort, PAI-2 is the most powerful prognostic factor (HR = 2.30; P = 0.001), followed by MMP-9 (HR = 2.09; P = 0.019) according to multivariate analysis. When combining PAI-2 and MMP-9, the most unfavorable prognostic group (low PAI-2 and high MMP-9 IHC expression levels) showed a 6.40-fold increased risk of a poor prognosis compared to the most favorable prognostic group (high PAI-2 and low MMP-9 IHC expression levels). PAI-2 and MMP-9 IHC panel could more precisely identify high risk patients in both derivation and validation cohort.\\n\\nCONCLUSIONS: We revealed PAI-2 as the most powerful prognostic marker among PA and MMP protease family even after considering their close relationships with each other. By utilizing a combination of PAI-2 and MMP-9, more precise prognostic information than merely using pathological stage alone can be obtained for lung cancer patients.", "link"=>"http://www.mendeley.com/research/plasminogen-activator-inhibitor2-plays-leading-prognostic-role-among-protease-families-nonsmall-cell", "reader_count"=>9, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Other"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Other"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Hungary"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2198545"], "description"=>"<p>(A) A representative lung adenocarcinoma with low IHC expression level of PAI-2 and high IHC expression levels of PAI-1, uPA, uPAR, MMP-2, and MMP-9, as detected by IHC. Photographs were taken at a magnification of 400×. Scale bars represent 100 μm. (B) Kaplan-Meier plots of overall survival relative to PAI-1, PAI-2, uPA, uPAR, MMP-2, and MMP-9 IHC expression levels in NSCLC. Low IHC expression level of PAI-2 was significantly associated with shorter overall survival (<i>P</i> < 0.001), as was high IHC expression levels of PAI-1, uPA, MMP-2, and MMP-9 (<i>P</i> = 0.015, <i>P</i> = 0.031, <i>P</i> = 0.041, <i>P</i> = 0.037, respectively). (C) Kaplan-Meier plots of disease-free survival relative to PAI-1, PAI-2, uPA, uPAR, MMP-2, and MMP-9 IHC expression levels in NSCLC. Low IHC expression level of PAI-2 was significantly associated with shorter disease-free survival (<i>P</i> < 0.001); high IHC expression levels of PAI-1, uPA, and MMP-9 was also significantly associated with shorter disease-free survival (<i>P</i> = 0.019, <i>P</i> = 0.017, <i>P</i> = 0.021, respectively).</p>", "links"=>[], "tags"=>["pai", "91 lung cancer patients.ResultsIn derivation cohort", "prognostic model analysis", "MMP protease family", "lung cancer patients", "immunohistochemical panel", "hr", "plasminogen activator family", "pa", "IHC expression levels", "marker", "prognostic group"], "article_id"=>1500642, "categories"=>["Biological Sciences"], "users"=>["Chia-Yi Su", "Yu-Peng Liu", "Chih-Jen Yang", "Yuan-Feng Lin", "Jean Chiou", "Li-Hsing Chi", "Jih-Jong Lee", "Alex T. H. Wu", "Pei-Jung Lu", "Ming-Shyan Huang", "Michael Hsiao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133411.g001", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_prognostic_value_of_markers_in_PA_and_MMP_families_in_derivation_cohort_with_98_NSCLC_cases_/1500642", "title"=>"The prognostic value of markers in PA and MMP families in derivation cohort with 98 NSCLC cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-31 04:39:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/2198547"], "description"=>"<p>(A) Kaplan-Meier plots and ROC curve of overall survival and disease-free survival for the combination of PAI-2 and MMP-9 as an IHC panel. Patients with high PAI-2 and low MMP-9 IHC expression levels had the most favorable prognosis, whereas patients with low PAI-2 and high MMP-9 IHC expression levels had the most unfavorable prognosis (<i>P</i> < 0.001 for both OS and DFS). Increase of area under curve (AUC) of ROC was observed after combining PAI-2 and MMP-9 as a panel in disease-free survival. In the heat map clustered by end-point survival status, patients who were dead at the end-point tended to have low PAI-2 and high MMP-9 IHC expression level. (B) Representative images of the usage of the PAI-2 and MMP-9 IHC panel in clinical NSCLC samples. Patient 1 had stage I adenocarcinoma with high PAI-2 and low MMP-9 IHC expression levels and was alive at the final follow up. In contrast, patient 2 had stage IV adenocarcinoma with low PAI-2 and high MMP-9 IHC expression levels and died 2 months after treatment commenced. Patients 3 and 4 were both diagnosed with stage III adenocarcinoma. Patient 3, who had high PAI-2 and low MMP-9 IHC expression levels, was alive and had no tumor recurrence at the final follow up; patient 4, who had low PAI-2 and high MMP-9 IHC expression levels, experienced tumor recurrence within 9 months and died 14 months after treatment commenced. Photographs were taken at a magnification of 400×. Scale bars represent 100 μm. (C) Kaplan-Meier plots and ROC curve of overall survival in validation cohort showed that patients with low PAI-2 IHC expression level (<i>P</i> = 0.002) or high MMP-9 IHC expression level (<i>P</i> = 0.035) had poor overall survival. When stratified by PAI-2 and MMP-9 IHC panel, high risk group patients had low PAI-2 and high MMP-9 IHC expression levels and low risk group patients had high PAI-2 and low MMP-9 IHC expression level (<i>P</i> < 0.001). Increase of area under curve (AUC) of ROC was observed after combining PAI-2 and MMP-9 as a panel. The heat map showed that patients who were dead at the end-point tended to have low PAI-2 and high MMP-9 IHC expression level.</p>", "links"=>[], "tags"=>["pai", "91 lung cancer patients.ResultsIn derivation cohort", "prognostic model analysis", "MMP protease family", "lung cancer patients", "immunohistochemical panel", "hr", "plasminogen activator family", "pa", "IHC expression levels", "marker", "prognostic group"], "article_id"=>1500644, "categories"=>["Biological Sciences"], "users"=>["Chia-Yi Su", "Yu-Peng Liu", "Chih-Jen Yang", "Yuan-Feng Lin", "Jean Chiou", "Li-Hsing Chi", "Jih-Jong Lee", "Alex T. H. Wu", "Pei-Jung Lu", "Ming-Shyan Huang", "Michael Hsiao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133411.g002", "stats"=>{"downloads"=>3, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_IHC_panel_comprising_PAI_2_and_MMP_9_provides_a_more_precise_prognostic_predictive_power_for_98_NSCLC_patients_in_derivation_cohort_and_91_NSCLC_patients_in_validation_cohort_/1500644", "title"=>"An IHC panel comprising PAI-2 and MMP-9 provides a more precise prognostic predictive power for 98 NSCLC patients in derivation cohort and 91 NSCLC patients in validation cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-31 04:39:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/2198548"], "description"=>"<p>**Correlation is significant at the 0.01 level (2-tailed).</p><p>*Correlation is significant at the 0.05 level (2-tailed).</p><p>PAI-1: plasminogen activator inhibitor-1; PAI-2: plasminogen activator inhibitor-2; uPA: urokinase-type plasminogen activator; uPAR: urokinase-type plasminogen activator receptor; MMP-2: matrix metalloproteinase 2; MMP-9: matrix metalloproteinase 9.</p><p>The correlations between IHC expression levels of PAI-1, PAI-2, uPA, uPAR, MMP-2, and MMP-9 analyzed by Spearman’s rank correlation analysis in derivation cohort with 98 NSCLC cases.</p>", "links"=>[], "tags"=>["pai", "91 lung cancer patients.ResultsIn derivation cohort", "prognostic model analysis", "MMP protease family", "lung cancer patients", "immunohistochemical panel", "hr", "plasminogen activator family", "pa", "IHC expression levels", "marker", "prognostic group"], "article_id"=>1500645, "categories"=>["Biological Sciences"], "users"=>["Chia-Yi Su", "Yu-Peng Liu", "Chih-Jen Yang", "Yuan-Feng Lin", "Jean Chiou", "Li-Hsing Chi", "Jih-Jong Lee", "Alex T. H. Wu", "Pei-Jung Lu", "Ming-Shyan Huang", "Michael Hsiao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133411.t001", "stats"=>{"downloads"=>4, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_correlations_between_IHC_expression_levels_of_PAI_1_PAI_2_uPA_uPAR_MMP_2_and_MMP_9_analyzed_by_Spearman_8217_s_rank_correlation_analysis_in_derivation_cohort_with_98_NSCLC_cases_/1500645", "title"=>"The correlations between IHC expression levels of PAI-1, PAI-2, uPA, uPAR, MMP-2, and MMP-9 analyzed by Spearman’s rank correlation analysis in derivation cohort with 98 NSCLC cases.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-31 04:39:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/2198549"], "description"=>"<p>*<i>P</i> value after Benjamini and Hochberg false discovery rate (FDR) procedure.</p><p>PAI-1: plasminogen activator inhibitor-1; PAI-2: plasminogen activator inhibitor-2; uPA: urokinase-type plasminogen activator; uPAR: urokinase-type plasminogen activator receptor; MMP-2: matrix metalloproteinase 2; MMP-9: matrix metalloproteinase 9.</p><p>Cox multivariate analysis with false discovery rate correction of PAI-1, PAI-2, uPA, uPAR, MMP-2 and MMP-9 IHC expression levels and pathological stage in derivation cohort with 98 NSCLC cases.</p>", "links"=>[], "tags"=>["pai", "91 lung cancer patients.ResultsIn derivation cohort", "prognostic model analysis", "MMP protease family", "lung cancer patients", "immunohistochemical panel", "hr", "plasminogen activator family", "pa", "IHC expression levels", "marker", "prognostic group"], "article_id"=>1500646, "categories"=>["Biological Sciences"], "users"=>["Chia-Yi Su", "Yu-Peng Liu", "Chih-Jen Yang", "Yuan-Feng Lin", "Jean Chiou", "Li-Hsing Chi", "Jih-Jong Lee", "Alex T. H. Wu", "Pei-Jung Lu", "Ming-Shyan Huang", "Michael Hsiao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133411.t002", "stats"=>{"downloads"=>5, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cox_multivariate_analysis_with_false_discovery_rate_correction_of_PAI_1_PAI_2_uPA_uPAR_MMP_2_and_MMP_9_IHC_expression_levels_and_pathological_stage_in_derivation_cohort_with_98_NSCLC_cases_/1500646", "title"=>"Cox multivariate analysis with false discovery rate correction of PAI-1, PAI-2, uPA, uPAR, MMP-2 and MMP-9 IHC expression levels and pathological stage in derivation cohort with 98 NSCLC cases.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-31 04:39:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/2198550"], "description"=>"<p>PAI-1: plasminogen activator inhibitor-1; PAI-2: plasminogen activator inhibitor-2; uPA: urokinase-type plasminogen activator; uPAR: urokinase-type plasminogen activator receptor; MMP-2: matrix metalloproteinase 2; MMP-9: matrix metalloproteinase 9.</p><p>Cox univariate and multivariate analyses of disease-free survival in association with PAI-2 and MMP-9 IHC expression levels and pathological stage in derivation cohort with 98 NSCLC cases.</p>", "links"=>[], "tags"=>["pai", "91 lung cancer patients.ResultsIn derivation cohort", "prognostic model analysis", "MMP protease family", "lung cancer patients", "immunohistochemical panel", "hr", "plasminogen activator family", "pa", "IHC expression levels", "marker", "prognostic group"], "article_id"=>1500647, "categories"=>["Biological Sciences"], "users"=>["Chia-Yi Su", "Yu-Peng Liu", "Chih-Jen Yang", "Yuan-Feng Lin", "Jean Chiou", "Li-Hsing Chi", "Jih-Jong Lee", "Alex T. H. Wu", "Pei-Jung Lu", "Ming-Shyan Huang", "Michael Hsiao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133411.t003", "stats"=>{"downloads"=>7, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cox_univariate_and_multivariate_analyses_of_disease_free_survival_in_association_with_PAI_2_and_MMP_9_IHC_expression_levels_and_pathological_stage_in_derivation_cohort_with_98_NSCLC_cases_/1500647", "title"=>"Cox univariate and multivariate analyses of disease-free survival in association with PAI-2 and MMP-9 IHC expression levels and pathological stage in derivation cohort with 98 NSCLC cases.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-31 04:39:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/2198558", "https://ndownloader.figshare.com/files/2198559", "https://ndownloader.figshare.com/files/2198560", "https://ndownloader.figshare.com/files/2198561", "https://ndownloader.figshare.com/files/2198562", "https://ndownloader.figshare.com/files/2198563", "https://ndownloader.figshare.com/files/2198564", "https://ndownloader.figshare.com/files/2198565", "https://ndownloader.figshare.com/files/2198566", "https://ndownloader.figshare.com/files/2198567", "https://ndownloader.figshare.com/files/2198568", "https://ndownloader.figshare.com/files/2198569"], "description"=>"<div><p>Background</p><p>In lung cancer, uPA, its receptor (uPAR), and the inhibitors PAI-1 and PAI-2 of the plasminogen activator family interact with MMP-2 and MMP-9 of the MMP family to promote cancer progression. However, it remains undetermined which of these markers plays the most important role and may be the most useful indicator to stratify the patients by risk.</p><p>Methods</p><p>We determined the individual prognostic value of these 6 markers by analyzing a derivation cohort with 98 non-small cell lung cancer patients by immunohistochemical staining. The correlation between the IHC expression levels of these markers and disease prognosis was investigated, and an immunohistochemical panel for prognostic prediction was subsequently generated through prognostic model analysis. The value of the immunohistochemical panel was then verified by a validation cohort with 91 lung cancer patients.</p><p>Results</p><p>In derivation cohort, PAI-2 is the most powerful prognostic factor (HR = 2.30; <i>P</i> = 0.001), followed by MMP-9 (HR = 2.09; <i>P</i> = 0.019) according to multivariate analysis. When combining PAI-2 and MMP-9, the most unfavorable prognostic group (low PAI-2 and high MMP-9 IHC expression levels) showed a 6.40-fold increased risk of a poor prognosis compared to the most favorable prognostic group (high PAI-2 and low MMP-9 IHC expression levels). PAI-2 and MMP-9 IHC panel could more precisely identify high risk patients in both derivation and validation cohort.</p><p>Conclusions</p><p>We revealed PAI-2 as the most powerful prognostic marker among PA and MMP protease family even after considering their close relationships with each other. By utilizing a combination of PAI-2 and MMP-9, more precise prognostic information than merely using pathological stage alone can be obtained for lung cancer patients.</p></div>", "links"=>[], "tags"=>["pai", "91 lung cancer patients.ResultsIn derivation cohort", "prognostic model analysis", "MMP protease family", "lung cancer patients", "immunohistochemical panel", "hr", "plasminogen activator family", "pa", "IHC expression levels", "marker", "prognostic group"], "article_id"=>1500654, "categories"=>["Biological Sciences"], "users"=>["Chia-Yi Su", "Yu-Peng Liu", "Chih-Jen Yang", "Yuan-Feng Lin", "Jean Chiou", "Li-Hsing Chi", "Jih-Jong Lee", "Alex T. H. Wu", "Pei-Jung Lu", "Ming-Shyan Huang", "Michael Hsiao"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0133411.s001", "https://dx.doi.org/10.1371/journal.pone.0133411.s002", "https://dx.doi.org/10.1371/journal.pone.0133411.s003", "https://dx.doi.org/10.1371/journal.pone.0133411.s004", "https://dx.doi.org/10.1371/journal.pone.0133411.s005", "https://dx.doi.org/10.1371/journal.pone.0133411.s006", "https://dx.doi.org/10.1371/journal.pone.0133411.s007", "https://dx.doi.org/10.1371/journal.pone.0133411.s008", "https://dx.doi.org/10.1371/journal.pone.0133411.s009", "https://dx.doi.org/10.1371/journal.pone.0133411.s010", "https://dx.doi.org/10.1371/journal.pone.0133411.s011", "https://dx.doi.org/10.1371/journal.pone.0133411.s012"], "stats"=>{"downloads"=>49, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasminogen_Activator_Inhibitor_2_Plays_a_Leading_Prognostic_Role_among_Protease_Families_in_Non_Small_Cell_Lung_Cancer_/1500654", "title"=>"Plasminogen Activator Inhibitor-2 Plays a Leading Prognostic Role among Protease Families in Non-Small Cell Lung Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-07-31 04:39:04"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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