TIA-1 Cytotoxic Granule-Associated RNA Binding Protein Improves the Prognostic Performance of CD8 in Mismatch Repair-Proficient Colorectal Cancer
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{"title"=>"TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Inti", "last_name"=>"Zlobec", "scopus_author_id"=>"8543721800"}, {"first_name"=>"Eva", "last_name"=>"Karamitopoulou", "scopus_author_id"=>"6603237083"}, {"first_name"=>"Luigi", "last_name"=>"Terracciano", "scopus_author_id"=>"7005698867"}, {"first_name"=>"Salvatore", "last_name"=>"Piscuoglio", "scopus_author_id"=>"25723793000"}, {"first_name"=>"Giandomenica", "last_name"=>"Iezzi", "scopus_author_id"=>"7003332209"}, {"first_name"=>"Manuele Giuseppe", "last_name"=>"Muraro", "scopus_author_id"=>"36515218900"}, {"first_name"=>"Giulio", "last_name"=>"Spagnoli", "scopus_author_id"=>"7004445872"}, {"first_name"=>"Kristi", "last_name"=>"Baker", "scopus_author_id"=>"13605362900"}, {"first_name"=>"Alexandar", "last_name"=>"Tzankov", "scopus_author_id"=>"6701844288"}, {"first_name"=>"Alessandro", "last_name"=>"Lugli", "scopus_author_id"=>"6601912628"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"361019915", "sgr"=>"78650744474", "issn"=>"19326203", "pmid"=>"21179245", "scopus"=>"2-s2.0-78650744474", "doi"=>"10.1371/journal.pone.0014282", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"0ecc1ab8-9a63-3bf1-ade3-596379d0a413", "abstract"=>"BACKGROUND: Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Colorectal cancers from a test (n=1197) and external validation (n=209) cohort of MMR-proficient colorectal cancers were mounted onto single and multiple punch tissue microarrays. Immunohistochemical quantification (score 0-3) was performed for CD3, CD4, CD8, CD45RO, CD68, CD163, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1 and TIA-1 tumor-infiltrating (TILs) reactive cells. Coexpression experiments on fresh colorectal cancer specimens using specific cell population markers were performed. In the test group, higher numbers of CD3+ (p<0.001), CD4+ (p=0.029), CD8+ (p<0.001), CD45RO+ (p=0.048), FoxP3+ (p<0.001), GranzymeB+ (p<0.001), iNOS+ (p=0.035), MUM1+ (p=0.014), PD1+ (p=0.034) and TIA-1+ TILs (p<0.001) were linked to favourable outcome. Adjusting for age, gender, TNM stage and post-operative therapy, higher CD8+ (p<0.001; HR (95%CI): 0.66 (0.64-0.68)) and TIA-1+ (p<0.001; HR (95%CI): 0.56 (0.5-0.6)) were independent prognostic factors. Moreover, among patients with CD8+ infiltrates, TIA-1 further stratified 355 (35.6%) patients into prognostic subgroups (p<0.001; HR (95%CI): 0.89 (95%CI: 0.8-0.9)). Results were confirmed on the validation cohort (p=0.006). TIA-1+ cells were mostly CD8+ (57%), but also stained for TCRγδ (22%), CD66b (13%) and only rarely for CD4+, macrophage and NK cell markers.\\n\\nCONCLUSIONS: TIA-1 adds prognostic information to TNM stage and adjuvant therapy in MMR-proficient colorectal cancer patients. The prognostic effect of CD8+ TILs is confounded by the presence of TIA-1+ which translates into improved risk stratification for approximately 35% of all patients with MMR-proficient colorectal cancers.", "link"=>"http://www.mendeley.com/research/tia1-cytotoxic-granuleassociated-rna-binding-protein-improves-prognostic-performance-cd8-mismatch-re", "reader_count"=>40, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>5, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>5, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>18, "Agricultural and Biological Sciences"=>10, "Psychology"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1, "Finland"=>1}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/813413"], "description"=>"<p>Kaplan-Meier survival curve shows the prognostic effect of CD8-negative, CD8+/TIA-1- and CD+8/TIA-1+ cells (Test Group).</p>", "links"=>[], "tags"=>["shows", "prognostic", "cells"], "article_id"=>483774, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.g005", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_survival_curve_shows_the_prognostic_effect_of_CD8_negative_CD8_TIA_1_and_CD_8_TIA_1_cells_Test_Group_/483774", "title"=>"Kaplan-Meier survival curve shows the prognostic effect of CD8-negative, CD8+/TIA-1- and CD+8/TIA-1+ cells (Test Group).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 21:54:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/813615"], "description"=>"<p>Characteristics of patients with mismatch repair-proficient colorectal cancer.</p>", "links"=>[], "tags"=>["patients", "mismatch", "repair-proficient", "colorectal"], "article_id"=>483976, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.t001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_patients_with_mismatch_repair_proficient_colorectal_cancer_/483976", "title"=>"Characteristics of patients with mismatch repair-proficient colorectal cancer.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 21:56:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/812927"], "description"=>"<p>Highlighted markers are those showing a significant association with prognosis.</p>", "links"=>[], "tags"=>["graphs", "illustrating", "prognostic"], "article_id"=>483285, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.g002", "stats"=>{"downloads"=>2, "page_views"=>169, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bar_graphs_illustrating_the_hazard_ratio_and_95_CI_for_the_prognostic_effect_of_each_biomarker_/483285", "title"=>"Bar graphs illustrating the hazard ratio and 95%CI for the prognostic effect of each biomarker.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 21:52:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/813307"], "description"=>"<p>Single cell suspensions obtained from freshly excised tumor specimens (n = 10) were surface stained with FITC- or APC-labeled antibodies specific for the indicated surface markers and intracellularly stained with PE-labeled anti-TIA-1 antibodies. A) Percentages of total TIA-1+ cells B) Percentages of CD8+ cells, TCRγδ cells, neutrophils (identified as CD66b+ cells), CD4+ cells, macrophages (identified as CD16+ CD56- cells), NK cells (CD16+ CD56+) and NKT cells (Vα24-Jα18 TCR+) observed within gated TIA-1+ cells. C) Representative dot-plot illustrating co-expression of TIA-1 and CD8 molecules within gated lymphocytes on total cells obtained from a clinical specimen. D) Percentages of TIA-1+ and TIA-1- cells within gated CD8+ cells.</p>", "links"=>[], "tags"=>["oncology/gastrointestinal cancers", "pathology/immunology", "pathology/surgical pathology"], "article_id"=>483668, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.g004", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TIA_1_expression_on_TILs_/483668", "title"=>"TIA-1 expression on TILs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 21:54:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/813570"], "description"=>"<p>Multiple Cox regression analysis showing the independent prognostic effect of CD8, TIA-1 and of TIA-1 among CD8+ cases (all p-values <0.001).</p>", "links"=>[], "tags"=>["cox", "regression", "prognostic", "tia-1", "cases", "p-values"], "article_id"=>483918, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.t002", "stats"=>{"downloads"=>8, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multiple_Cox_regression_analysis_showing_the_independent_prognostic_effect_of_CD8_TIA_1_and_of_TIA_1_among_CD8_cases_all_p_values_lt_0_001_/483918", "title"=>"Multiple Cox regression analysis showing the independent prognostic effect of CD8, TIA-1 and of TIA-1 among CD8+ cases (all p-values <0.001).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 21:55:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/812809"], "description"=>"<p>(A) 1420 colorectal cancers were mounted onto tissue microarrays and immunostained for 13 protein markers and mismatch repair (MMR) proteins. MMR-deficient tumors were excluded. (B) 221 colorectal cancers were mounted into a multiple-punch tissue microarray and immunostained for independent prognostic factors identified in Test Group. MMR-deficient tumors were excluded from analysis and validation of prognostic effects carried out on the remaining 209 patients.</p>", "links"=>[], "tags"=>["oncology/gastrointestinal cancers", "pathology/immunology", "pathology/surgical pathology"], "article_id"=>483161, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_study_design_/483161", "title"=>"Overview of study design.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 21:51:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/813116"], "description"=>"<p>A) CD3, B) CD4, C) CD8, D) CD45RO, E) FoxP3, F) Granzyme B, G) iNOS, H) MUM1, I) PD1, J) TIA-1.</p>", "links"=>[], "tags"=>["immunostains", "biomarkers", "prognostic"], "article_id"=>483478, "categories"=>["Immunology", "Medicine", "Cancer"], "users"=>["Inti Zlobec", "Eva Karamitopoulou", "Luigi Terracciano", "Salvatore Piscuoglio", "Giandomenica Iezzi", "Manuele Giuseppe Muraro", "Giulio Spagnoli", "Kristi Baker", "Alexandar Tzankov", "Alessandro Lugli"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014282.g003", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_immunostains_for_biomarkers_with_prognostic_significance_in_the_Test_Group_/483478", "title"=>"Representative immunostains for biomarkers with prognostic significance in the Test Group.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 21:53:19"}

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