Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02-05

AUTHORS

Maarit Ahtiainen, Erkki-Ville Wirta, Teijo Kuopio, Toni Seppälä, Juha Rantala, Jukka-Pekka Mecklin, Jan Böhm

ABSTRACT

The CD274 (programmed cell death ligand-1, PD-L1)/PDCD1 (programmed cell death-1, PD-1) pathway is crucial suppressor of the cytotoxic immune response. Antibodies targeting CD274 or PDCD1 have been revealed to be effective in several malignancies. In colorectal cancer, the response to CD274/PDCD1 blockage is associated with microsatellite instability. However, the value of CD274/PDCD1 for predicting response to treatment or survival benefit is still unclear. The aims of the study were (1) to clarify differences in immune microenvironment and expression of checkpoint proteins (CD274/PDCD1) in DNA mismatch repair-proficient, mismatch repair-deficient, and hereditary Lynch syndrome-associated colorectal cancer, and (2) to assess the prognostic value of these factors and their combinations. Ninety-four mismatch repair-deficient colorectal cancers, 100 age, sex, and AJCC/UICC stage-matched mismatch repair-proficient colorectal cancers, and 48 Lynch syndrome-associated colorectal cancers were analyzed. Using whole section samples, detailed analysis of immune cell score, PDCD1, and CD274 expression was performed. Overlapping of CD274 expression in tumor and immune cells was almost complete (95%). Immune cell score and CD274/PDCD1 positivity were significantly more frequent in mismatch repair-deficient than in mismatch repair-proficient colorectal cancers (70% vs. 41% (high immune cell score); 81% vs. 49% (PDCD1high), 23% vs. 1% (CD274 on tumor cells) and 68% vs. 30% (CD274 on immune cells), P < 0.001), and were associated strongly with each other. Although the independent impact of immune cell score, PDCD1, and CD274 on immune cells was moderate, the immunoprofile parameter combining the above three factors appeared to be a strong independent prognostic factor for disease-specific survival and overall survival (P = 0.001) and had suggestive impact on disease-free survival (P = 0.011). Our results encourage the use of immune cell score analysis together with PDCD1 and CD274 detection to improve the prognostic evaluation of colorectal cancer patients. Particularly, the analyses from whole tissue sections are encouraged to allow reliable and cell-specific analyses of CD274 expression. More... »

PAGES

1

References to SciGraph publications

  • 2016-09. PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes in MODERN PATHOLOGY
  • 2016-06. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues in INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
  • 2018-01. Redefine statistical significance in NATURE HUMAN BEHAVIOUR
  • 2015-06. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer in BRITISH JOURNAL OF CANCER
  • 2016-01. Practical issues related to uterine pathology: in situ and invasive cervical glandular lesions and their benign mimics: emphasis on cytology–histology correlation and interpretive pitfalls in MODERN PATHOLOGY
  • 2016-12. Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer in MOLECULAR CANCER
  • 2017-07. Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer in CANCER IMMUNOLOGY, IMMUNOTHERAPY
  • 2012-04. The immune contexture in human tumours: impact on clinical outcome in NATURE REVIEWS CANCER
  • 2016-08. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers in BRITISH JOURNAL OF CANCER
  • 2017-12. QuPath: Open source software for digital pathology image analysis in SCIENTIFIC REPORTS
  • 2016-05. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy in NATURE REVIEWS CANCER
  • 2018-12. Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? in CELL & BIOSCIENCE
  • 2015-04. Anti-programmed cell death protein-1/ligand-1 therapy in different cancers in BRITISH JOURNAL OF CANCER
  • 2019-04. Distinct contribution of PD-L1 suppression by spatial expression of PD-L1 on tumor and non-tumor cells in CELLULAR & MOLECULAR IMMUNOLOGY
  • 2009-09. Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations in MODERN PATHOLOGY
  • 2002-11. Cancer immunoediting: from immunosurveillance to tumor escape in NATURE IMMUNOLOGY
  • 2012-04. The blockade of immune checkpoints in cancer immunotherapy in NATURE REVIEWS CANCER
  • 2015-12. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy in GENOME BIOLOGY
  • 2016-12. Biomarkers immune monitoring technology primer: Immunoscore® Colon in JOURNAL FOR IMMUNOTHERAPY OF CANCER
  • 2016-05. Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients in VIRCHOWS ARCHIV
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41379-019-0219-7

    DOI

    http://dx.doi.org/10.1038/s41379-019-0219-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111918576

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30723299


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Immunology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Central Finland Health Care District", 
              "id": "https://www.grid.ac/institutes/grid.460356.2", 
              "name": [
                "Department of Education and Research, Central Finland Central Hospital, Jyv\u00e4skyl\u00e4, Finland. maarit.ahtiainen@ksshp.fi."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ahtiainen", 
            "givenName": "Maarit", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Tampere University Hospital", 
              "id": "https://www.grid.ac/institutes/grid.412330.7", 
              "name": [
                "Department of Surgery, Central Finland Central Hospital, Jyv\u00e4skyl\u00e4, Finland.", 
                "Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wirta", 
            "givenName": "Erkki-Ville", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Jyv\u00e4skyl\u00e4", 
              "id": "https://www.grid.ac/institutes/grid.9681.6", 
              "name": [
                "Department of Pathology, Central Finland Central Hospital, Jyv\u00e4skyl\u00e4, Finland.", 
                "Biological and Environmental Science, University of Jyv\u00e4skyl\u00e4, Jyv\u00e4skyl\u00e4, Finland."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kuopio", 
            "givenName": "Teijo", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Gastrointestinal Surgery, Abdominal Center, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Sepp\u00e4l\u00e4", 
            "givenName": "Toni", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Cancer Research, Misvik Biology, Turku, Finland."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rantala", 
            "givenName": "Juha", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Jyv\u00e4skyl\u00e4", 
              "id": "https://www.grid.ac/institutes/grid.9681.6", 
              "name": [
                "Department of Education and Research, Central Finland Central Hospital, Jyv\u00e4skyl\u00e4, Finland.", 
                "Faculty of Sport and Health Sciences, University of Jyv\u00e4skyl\u00e4, Jyv\u00e4skyl\u00e4, Finland."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mecklin", 
            "givenName": "Jukka-Pekka", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Central Finland Health Care District", 
              "id": "https://www.grid.ac/institutes/grid.460356.2", 
              "name": [
                "Department of Pathology, Central Finland Central Hospital, Jyv\u00e4skyl\u00e4, Finland."
              ], 
              "type": "Organization"
            }, 
            "familyName": "B\u00f6hm", 
            "givenName": "Jan", 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/modpathol.2015.138", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000085054", 
              "https://doi.org/10.1038/modpathol.2015.138"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.2015.160", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004641323", 
              "https://doi.org/10.1038/bjc.2015.160"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.coph.2015.05.011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004898839"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-15-0255", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007025850"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc.2016.36", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012106897", 
              "https://doi.org/10.1038/nrc.2016.36"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2008.19.6147", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013118343"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni1102-991", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013709887", 
              "https://doi.org/10.1038/ni1102-991"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni1102-991", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013709887", 
              "https://doi.org/10.1038/ni1102-991"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.2009.80", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015474458", 
              "https://doi.org/10.1038/modpathol.2009.80"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.2009.80", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015474458", 
              "https://doi.org/10.1038/modpathol.2009.80"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/path.2774", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017317749"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/path.2774", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017317749"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/scitranslmed.3003689", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018365419"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1155/2010/170432", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018713589"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2009.26.7609", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020897568"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1129139", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021857158"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.2016.95", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022975344", 
              "https://doi.org/10.1038/modpathol.2016.95"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/carcin/bgm228", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023210813"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/1097-0142(20010615)91:12<2417::aid-cncr1276>3.0.co;2-u", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023347319"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-13-2830", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023358367"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s40425-016-0161-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026530170", 
              "https://doi.org/10.1186/s40425-016-0161-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s40425-016-0161-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026530170", 
              "https://doi.org/10.1186/s40425-016-0161-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1136/gutjnl-2016-311421", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026623023"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00428-016-1910-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026762564", 
              "https://doi.org/10.1007/s00428-016-1910-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10147-016-0959-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026945063", 
              "https://doi.org/10.1007/s10147-016-0959-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10147-016-0959-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026945063", 
              "https://doi.org/10.1007/s10147-016-0959-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/2159-8290.cd-14-0863", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029393757"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2010.30.5425", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030439270"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.celrep.2016.03.075", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030720145"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.2015.124", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031527720", 
              "https://doi.org/10.1038/bjc.2015.124"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.18632/oncotarget.13207", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033286470"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-09-1438", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033591305"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molmed.2015.11.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034412182"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc3245", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034518617", 
              "https://doi.org/10.1038/nrc3245"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/hmg/10.7.735", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036410802"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.5858/arpa.2015-0506-sa", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036718208"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.2016.211", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037442310", 
              "https://doi.org/10.1038/bjc.2016.211"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-015-0620-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037738332", 
              "https://doi.org/10.1186/s13059-015-0620-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-015-0620-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037738332", 
              "https://doi.org/10.1186/s13059-015-0620-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1001/jamaoncol.2016.3015", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039157573"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12943-016-0539-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040250361", 
              "https://doi.org/10.1186/s12943-016-0539-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12943-016-0539-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040250361", 
              "https://doi.org/10.1186/s12943-016-0539-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/path.4287", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040977925"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/pas.0000000000000504", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041802389"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/pas.0000000000000504", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041802389"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejmoa1200690", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042896583"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.95.12.6870", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043191674"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1399-0004.2009.01230.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043586216"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1399-0004.2009.01230.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043586216"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejmoa1200694", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047413837"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc3239", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047946992", 
              "https://doi.org/10.1038/nrc3239"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.immuni.2016.02.025", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049973998"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-14-3051", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050762714"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejmoa1500596", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053017729"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/pcmr.12340", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053525666"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/annonc/mdv489", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1059394581"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1136/gutjnl-2016-311403", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062813712"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1001/jamaoncol.2017.0013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084006036"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00262-017-1999-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084803794", 
              "https://doi.org/10.1007/s00262-017-1999-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00262-017-1999-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084803794", 
              "https://doi.org/10.1007/s00262-017-1999-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2016.70.7547", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084826430"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/cjp2.71", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085200841"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.aan6733", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085942187"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.aan6733", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085942187"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/po.16.00005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1090382318"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s1470-2045(17)30422-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1090805001"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41562-017-0189-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091412321", 
              "https://doi.org/10.1038/s41562-017-0189-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41562-017-0189-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091412321", 
              "https://doi.org/10.1038/s41562-017-0189-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.prp.2017.09.012", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091834526"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41598-017-17204-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1093066740", 
              "https://doi.org/10.1038/s41598-017-17204-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41423-018-0021-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101674173", 
              "https://doi.org/10.1038/s41423-018-0021-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41423-018-0021-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101674173", 
              "https://doi.org/10.1038/s41423-018-0021-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41423-018-0021-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101674173", 
              "https://doi.org/10.1038/s41423-018-0021-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41423-018-0021-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101674173", 
              "https://doi.org/10.1038/s41423-018-0021-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13578-018-0232-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103750729", 
              "https://doi.org/10.1186/s13578-018-0232-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13578-018-0232-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103750729", 
              "https://doi.org/10.1186/s13578-018-0232-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0140-6736(18)30789-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103931047"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-02-05", 
        "datePublishedReg": "2019-02-05", 
        "description": "The CD274 (programmed cell death ligand-1, PD-L1)/PDCD1 (programmed cell death-1, PD-1) pathway is crucial suppressor of the cytotoxic immune response. Antibodies targeting CD274 or PDCD1 have been revealed to be effective in several malignancies. In colorectal cancer, the response to CD274/PDCD1 blockage is associated with microsatellite instability. However, the value of CD274/PDCD1 for predicting response to treatment or survival benefit is still unclear. The aims of the study were (1) to clarify differences in immune microenvironment and expression of checkpoint proteins (CD274/PDCD1) in DNA mismatch repair-proficient, mismatch repair-deficient, and hereditary Lynch syndrome-associated colorectal cancer, and (2) to assess the prognostic value of these factors and their combinations. Ninety-four mismatch repair-deficient colorectal cancers, 100 age, sex, and AJCC/UICC stage-matched mismatch repair-proficient colorectal cancers, and 48 Lynch syndrome-associated colorectal cancers were analyzed. Using whole section samples, detailed analysis of immune cell score, PDCD1, and CD274 expression was performed. Overlapping of CD274 expression in tumor and immune cells was almost complete (95%). Immune cell score and CD274/PDCD1 positivity were significantly more frequent in mismatch repair-deficient than in mismatch repair-proficient colorectal cancers (70% vs. 41% (high immune cell score); 81% vs. 49% (PDCD1high), 23% vs. 1% (CD274 on tumor cells) and 68% vs. 30% (CD274 on immune cells), P\u2009<\u20090.001), and were associated strongly with each other. Although the independent impact of immune cell score, PDCD1, and CD274 on immune cells was moderate, the immunoprofile parameter combining the above three factors appeared to be a strong independent prognostic factor for disease-specific survival and overall survival (P\u2009=\u20090.001) and had suggestive impact on disease-free survival (P\u2009=\u20090.011). Our results encourage the use of immune cell score analysis together with PDCD1 and CD274 detection to improve the prognostic evaluation of colorectal cancer patients. Particularly, the analyses from whole tissue sections are encouraged to allow reliable and cell-specific analyses of CD274 expression.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/s41379-019-0219-7", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1098208", 
            "issn": [
              "0893-3952", 
              "1530-0285"
            ], 
            "name": "Modern Pathology", 
            "type": "Periodical"
          }
        ], 
        "name": "Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status", 
        "pagination": "1", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "f1b4e25bbcf7e1367cb7e171f2d507cbef226495c3fd581f086e35068f16333e"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30723299"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "8806605"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41379-019-0219-7"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1111918576"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41379-019-0219-7", 
          "https://app.dimensions.ai/details/publication/pub.1111918576"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T09:01", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000330_0000000330/records_116375_00000000.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/s41379-019-0219-7"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41379-019-0219-7'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41379-019-0219-7'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41379-019-0219-7'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41379-019-0219-7'


     

    This table displays all metadata directly associated to this object as RDF triples.

    316 TRIPLES      21 PREDICATES      87 URIs      18 LITERALS      7 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41379-019-0219-7 schema:about anzsrc-for:11
    2 anzsrc-for:1107
    3 schema:author N8a7a2abe3ca24aee965e133919283a03
    4 schema:citation sg:pub.10.1007/s00262-017-1999-6
    5 sg:pub.10.1007/s00428-016-1910-4
    6 sg:pub.10.1007/s10147-016-0959-z
    7 sg:pub.10.1038/bjc.2015.124
    8 sg:pub.10.1038/bjc.2015.160
    9 sg:pub.10.1038/bjc.2016.211
    10 sg:pub.10.1038/modpathol.2009.80
    11 sg:pub.10.1038/modpathol.2015.138
    12 sg:pub.10.1038/modpathol.2016.95
    13 sg:pub.10.1038/ni1102-991
    14 sg:pub.10.1038/nrc.2016.36
    15 sg:pub.10.1038/nrc3239
    16 sg:pub.10.1038/nrc3245
    17 sg:pub.10.1038/s41423-018-0021-3
    18 sg:pub.10.1038/s41562-017-0189-z
    19 sg:pub.10.1038/s41598-017-17204-5
    20 sg:pub.10.1186/s12943-016-0539-x
    21 sg:pub.10.1186/s13059-015-0620-6
    22 sg:pub.10.1186/s13578-018-0232-4
    23 sg:pub.10.1186/s40425-016-0161-x
    24 https://doi.org/10.1001/jamaoncol.2016.3015
    25 https://doi.org/10.1001/jamaoncol.2017.0013
    26 https://doi.org/10.1002/1097-0142(20010615)91:12<2417::aid-cncr1276>3.0.co;2-u
    27 https://doi.org/10.1002/cjp2.71
    28 https://doi.org/10.1002/path.2774
    29 https://doi.org/10.1002/path.4287
    30 https://doi.org/10.1016/j.celrep.2016.03.075
    31 https://doi.org/10.1016/j.coph.2015.05.011
    32 https://doi.org/10.1016/j.immuni.2016.02.025
    33 https://doi.org/10.1016/j.molmed.2015.11.003
    34 https://doi.org/10.1016/j.prp.2017.09.012
    35 https://doi.org/10.1016/s0140-6736(18)30789-x
    36 https://doi.org/10.1016/s1470-2045(17)30422-9
    37 https://doi.org/10.1056/nejmoa1200690
    38 https://doi.org/10.1056/nejmoa1200694
    39 https://doi.org/10.1056/nejmoa1500596
    40 https://doi.org/10.1073/pnas.95.12.6870
    41 https://doi.org/10.1093/annonc/mdv489
    42 https://doi.org/10.1093/carcin/bgm228
    43 https://doi.org/10.1093/hmg/10.7.735
    44 https://doi.org/10.1097/pas.0000000000000504
    45 https://doi.org/10.1111/j.1399-0004.2009.01230.x
    46 https://doi.org/10.1111/pcmr.12340
    47 https://doi.org/10.1126/science.1129139
    48 https://doi.org/10.1126/science.aan6733
    49 https://doi.org/10.1126/scitranslmed.3003689
    50 https://doi.org/10.1136/gutjnl-2016-311403
    51 https://doi.org/10.1136/gutjnl-2016-311421
    52 https://doi.org/10.1155/2010/170432
    53 https://doi.org/10.1158/0008-5472.can-14-3051
    54 https://doi.org/10.1158/0008-5472.can-15-0255
    55 https://doi.org/10.1158/1078-0432.ccr-09-1438
    56 https://doi.org/10.1158/1078-0432.ccr-13-2830
    57 https://doi.org/10.1158/2159-8290.cd-14-0863
    58 https://doi.org/10.1200/jco.2008.19.6147
    59 https://doi.org/10.1200/jco.2009.26.7609
    60 https://doi.org/10.1200/jco.2010.30.5425
    61 https://doi.org/10.1200/jco.2016.70.7547
    62 https://doi.org/10.1200/po.16.00005
    63 https://doi.org/10.18632/oncotarget.13207
    64 https://doi.org/10.5858/arpa.2015-0506-sa
    65 schema:datePublished 2019-02-05
    66 schema:datePublishedReg 2019-02-05
    67 schema:description The CD274 (programmed cell death ligand-1, PD-L1)/PDCD1 (programmed cell death-1, PD-1) pathway is crucial suppressor of the cytotoxic immune response. Antibodies targeting CD274 or PDCD1 have been revealed to be effective in several malignancies. In colorectal cancer, the response to CD274/PDCD1 blockage is associated with microsatellite instability. However, the value of CD274/PDCD1 for predicting response to treatment or survival benefit is still unclear. The aims of the study were (1) to clarify differences in immune microenvironment and expression of checkpoint proteins (CD274/PDCD1) in DNA mismatch repair-proficient, mismatch repair-deficient, and hereditary Lynch syndrome-associated colorectal cancer, and (2) to assess the prognostic value of these factors and their combinations. Ninety-four mismatch repair-deficient colorectal cancers, 100 age, sex, and AJCC/UICC stage-matched mismatch repair-proficient colorectal cancers, and 48 Lynch syndrome-associated colorectal cancers were analyzed. Using whole section samples, detailed analysis of immune cell score, PDCD1, and CD274 expression was performed. Overlapping of CD274 expression in tumor and immune cells was almost complete (95%). Immune cell score and CD274/PDCD1 positivity were significantly more frequent in mismatch repair-deficient than in mismatch repair-proficient colorectal cancers (70% vs. 41% (high immune cell score); 81% vs. 49% (PDCD1<sup>high</sup>), 23% vs. 1% (CD274 on tumor cells) and 68% vs. 30% (CD274 on immune cells), P &lt; 0.001), and were associated strongly with each other. Although the independent impact of immune cell score, PDCD1, and CD274 on immune cells was moderate, the immunoprofile parameter combining the above three factors appeared to be a strong independent prognostic factor for disease-specific survival and overall survival (P = 0.001) and had suggestive impact on disease-free survival (P = 0.011). Our results encourage the use of immune cell score analysis together with PDCD1 and CD274 detection to improve the prognostic evaluation of colorectal cancer patients. Particularly, the analyses from whole tissue sections are encouraged to allow reliable and cell-specific analyses of CD274 expression.
    68 schema:genre research_article
    69 schema:inLanguage en
    70 schema:isAccessibleForFree false
    71 schema:isPartOf sg:journal.1098208
    72 schema:name Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status
    73 schema:pagination 1
    74 schema:productId N97e068ba4cfd47548341a45f5b0f4e7a
    75 Nca4069b7f38548df9c4000dbbdc51956
    76 Ndd271fc16a094b1b9614b220f363de20
    77 Ndec6ef58cc02498a85cc344d1fdad576
    78 Nf538220ba5bb4f6c9d58f6377923ca15
    79 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111918576
    80 https://doi.org/10.1038/s41379-019-0219-7
    81 schema:sdDatePublished 2019-04-11T09:01
    82 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    83 schema:sdPublisher Nc2bf0421082e4d76b31e9409a99f6f4e
    84 schema:url https://www.nature.com/articles/s41379-019-0219-7
    85 sgo:license sg:explorer/license/
    86 sgo:sdDataset articles
    87 rdf:type schema:ScholarlyArticle
    88 N07fe34654dae4f4b8f5e2a94167f6195 schema:affiliation N2f8231e00e5e4ce4994e6f9211af8008
    89 schema:familyName Seppälä
    90 schema:givenName Toni
    91 rdf:type schema:Person
    92 N20ff6c9de1fd42b9a8e6eab9d48d4c29 rdf:first Nc9ed3285f1e84870969cafc79fa119ac
    93 rdf:rest N7b91b66d985e48e18a53dfc6048b932c
    94 N24ca7cfe37dc439dba58937ff96454cc schema:name Cancer Research, Misvik Biology, Turku, Finland.
    95 rdf:type schema:Organization
    96 N2ddf02880ee940f49da4f8d6ecd8f025 schema:affiliation N24ca7cfe37dc439dba58937ff96454cc
    97 schema:familyName Rantala
    98 schema:givenName Juha
    99 rdf:type schema:Person
    100 N2e36916a915e4059b3e9404784b2f4b4 rdf:first N2ddf02880ee940f49da4f8d6ecd8f025
    101 rdf:rest N20ff6c9de1fd42b9a8e6eab9d48d4c29
    102 N2f8231e00e5e4ce4994e6f9211af8008 schema:name Department of Gastrointestinal Surgery, Abdominal Center, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
    103 rdf:type schema:Organization
    104 N3e1ab44e95944fecae6971ff13c70009 rdf:first N07fe34654dae4f4b8f5e2a94167f6195
    105 rdf:rest N2e36916a915e4059b3e9404784b2f4b4
    106 N5b109b85db224e8081fb7cfddd6c25bb rdf:first Nf503d05e7c3d430693d3b5f67aa7419f
    107 rdf:rest Nfca0e40c656947218c48f691e0a09442
    108 N673ca9ff99cc4f42bc3d154bdaad32a3 schema:affiliation https://www.grid.ac/institutes/grid.460356.2
    109 schema:familyName Ahtiainen
    110 schema:givenName Maarit
    111 rdf:type schema:Person
    112 N7b91b66d985e48e18a53dfc6048b932c rdf:first N8bfb330963f548528c99c51ebf8dda42
    113 rdf:rest rdf:nil
    114 N8a7a2abe3ca24aee965e133919283a03 rdf:first N673ca9ff99cc4f42bc3d154bdaad32a3
    115 rdf:rest N5b109b85db224e8081fb7cfddd6c25bb
    116 N8bfb330963f548528c99c51ebf8dda42 schema:affiliation https://www.grid.ac/institutes/grid.460356.2
    117 schema:familyName Böhm
    118 schema:givenName Jan
    119 rdf:type schema:Person
    120 N97e068ba4cfd47548341a45f5b0f4e7a schema:name readcube_id
    121 schema:value f1b4e25bbcf7e1367cb7e171f2d507cbef226495c3fd581f086e35068f16333e
    122 rdf:type schema:PropertyValue
    123 Nc2bf0421082e4d76b31e9409a99f6f4e schema:name Springer Nature - SN SciGraph project
    124 rdf:type schema:Organization
    125 Nc9ed3285f1e84870969cafc79fa119ac schema:affiliation https://www.grid.ac/institutes/grid.9681.6
    126 schema:familyName Mecklin
    127 schema:givenName Jukka-Pekka
    128 rdf:type schema:Person
    129 Nca4069b7f38548df9c4000dbbdc51956 schema:name dimensions_id
    130 schema:value pub.1111918576
    131 rdf:type schema:PropertyValue
    132 Ndd271fc16a094b1b9614b220f363de20 schema:name pubmed_id
    133 schema:value 30723299
    134 rdf:type schema:PropertyValue
    135 Ndec6ef58cc02498a85cc344d1fdad576 schema:name doi
    136 schema:value 10.1038/s41379-019-0219-7
    137 rdf:type schema:PropertyValue
    138 Ne9bfeddd335d46e4be6a51aabfab0e74 schema:affiliation https://www.grid.ac/institutes/grid.9681.6
    139 schema:familyName Kuopio
    140 schema:givenName Teijo
    141 rdf:type schema:Person
    142 Nf503d05e7c3d430693d3b5f67aa7419f schema:affiliation https://www.grid.ac/institutes/grid.412330.7
    143 schema:familyName Wirta
    144 schema:givenName Erkki-Ville
    145 rdf:type schema:Person
    146 Nf538220ba5bb4f6c9d58f6377923ca15 schema:name nlm_unique_id
    147 schema:value 8806605
    148 rdf:type schema:PropertyValue
    149 Nfca0e40c656947218c48f691e0a09442 rdf:first Ne9bfeddd335d46e4be6a51aabfab0e74
    150 rdf:rest N3e1ab44e95944fecae6971ff13c70009
    151 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    152 schema:name Medical and Health Sciences
    153 rdf:type schema:DefinedTerm
    154 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
    155 schema:name Immunology
    156 rdf:type schema:DefinedTerm
    157 sg:journal.1098208 schema:issn 0893-3952
    158 1530-0285
    159 schema:name Modern Pathology
    160 rdf:type schema:Periodical
    161 sg:pub.10.1007/s00262-017-1999-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084803794
    162 https://doi.org/10.1007/s00262-017-1999-6
    163 rdf:type schema:CreativeWork
    164 sg:pub.10.1007/s00428-016-1910-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026762564
    165 https://doi.org/10.1007/s00428-016-1910-4
    166 rdf:type schema:CreativeWork
    167 sg:pub.10.1007/s10147-016-0959-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1026945063
    168 https://doi.org/10.1007/s10147-016-0959-z
    169 rdf:type schema:CreativeWork
    170 sg:pub.10.1038/bjc.2015.124 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031527720
    171 https://doi.org/10.1038/bjc.2015.124
    172 rdf:type schema:CreativeWork
    173 sg:pub.10.1038/bjc.2015.160 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004641323
    174 https://doi.org/10.1038/bjc.2015.160
    175 rdf:type schema:CreativeWork
    176 sg:pub.10.1038/bjc.2016.211 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037442310
    177 https://doi.org/10.1038/bjc.2016.211
    178 rdf:type schema:CreativeWork
    179 sg:pub.10.1038/modpathol.2009.80 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015474458
    180 https://doi.org/10.1038/modpathol.2009.80
    181 rdf:type schema:CreativeWork
    182 sg:pub.10.1038/modpathol.2015.138 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000085054
    183 https://doi.org/10.1038/modpathol.2015.138
    184 rdf:type schema:CreativeWork
    185 sg:pub.10.1038/modpathol.2016.95 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022975344
    186 https://doi.org/10.1038/modpathol.2016.95
    187 rdf:type schema:CreativeWork
    188 sg:pub.10.1038/ni1102-991 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013709887
    189 https://doi.org/10.1038/ni1102-991
    190 rdf:type schema:CreativeWork
    191 sg:pub.10.1038/nrc.2016.36 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012106897
    192 https://doi.org/10.1038/nrc.2016.36
    193 rdf:type schema:CreativeWork
    194 sg:pub.10.1038/nrc3239 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047946992
    195 https://doi.org/10.1038/nrc3239
    196 rdf:type schema:CreativeWork
    197 sg:pub.10.1038/nrc3245 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034518617
    198 https://doi.org/10.1038/nrc3245
    199 rdf:type schema:CreativeWork
    200 sg:pub.10.1038/s41423-018-0021-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101674173
    201 https://doi.org/10.1038/s41423-018-0021-3
    202 rdf:type schema:CreativeWork
    203 sg:pub.10.1038/s41562-017-0189-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1091412321
    204 https://doi.org/10.1038/s41562-017-0189-z
    205 rdf:type schema:CreativeWork
    206 sg:pub.10.1038/s41598-017-17204-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1093066740
    207 https://doi.org/10.1038/s41598-017-17204-5
    208 rdf:type schema:CreativeWork
    209 sg:pub.10.1186/s12943-016-0539-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1040250361
    210 https://doi.org/10.1186/s12943-016-0539-x
    211 rdf:type schema:CreativeWork
    212 sg:pub.10.1186/s13059-015-0620-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037738332
    213 https://doi.org/10.1186/s13059-015-0620-6
    214 rdf:type schema:CreativeWork
    215 sg:pub.10.1186/s13578-018-0232-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103750729
    216 https://doi.org/10.1186/s13578-018-0232-4
    217 rdf:type schema:CreativeWork
    218 sg:pub.10.1186/s40425-016-0161-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1026530170
    219 https://doi.org/10.1186/s40425-016-0161-x
    220 rdf:type schema:CreativeWork
    221 https://doi.org/10.1001/jamaoncol.2016.3015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039157573
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1001/jamaoncol.2017.0013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084006036
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1002/1097-0142(20010615)91:12<2417::aid-cncr1276>3.0.co;2-u schema:sameAs https://app.dimensions.ai/details/publication/pub.1023347319
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1002/cjp2.71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085200841
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1002/path.2774 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017317749
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1002/path.4287 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040977925
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1016/j.celrep.2016.03.075 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030720145
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1016/j.coph.2015.05.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004898839
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.1016/j.immuni.2016.02.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049973998
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.1016/j.molmed.2015.11.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034412182
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.1016/j.prp.2017.09.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091834526
    242 rdf:type schema:CreativeWork
    243 https://doi.org/10.1016/s0140-6736(18)30789-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1103931047
    244 rdf:type schema:CreativeWork
    245 https://doi.org/10.1016/s1470-2045(17)30422-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090805001
    246 rdf:type schema:CreativeWork
    247 https://doi.org/10.1056/nejmoa1200690 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042896583
    248 rdf:type schema:CreativeWork
    249 https://doi.org/10.1056/nejmoa1200694 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047413837
    250 rdf:type schema:CreativeWork
    251 https://doi.org/10.1056/nejmoa1500596 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053017729
    252 rdf:type schema:CreativeWork
    253 https://doi.org/10.1073/pnas.95.12.6870 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043191674
    254 rdf:type schema:CreativeWork
    255 https://doi.org/10.1093/annonc/mdv489 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059394581
    256 rdf:type schema:CreativeWork
    257 https://doi.org/10.1093/carcin/bgm228 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023210813
    258 rdf:type schema:CreativeWork
    259 https://doi.org/10.1093/hmg/10.7.735 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036410802
    260 rdf:type schema:CreativeWork
    261 https://doi.org/10.1097/pas.0000000000000504 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041802389
    262 rdf:type schema:CreativeWork
    263 https://doi.org/10.1111/j.1399-0004.2009.01230.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1043586216
    264 rdf:type schema:CreativeWork
    265 https://doi.org/10.1111/pcmr.12340 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053525666
    266 rdf:type schema:CreativeWork
    267 https://doi.org/10.1126/science.1129139 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021857158
    268 rdf:type schema:CreativeWork
    269 https://doi.org/10.1126/science.aan6733 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085942187
    270 rdf:type schema:CreativeWork
    271 https://doi.org/10.1126/scitranslmed.3003689 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018365419
    272 rdf:type schema:CreativeWork
    273 https://doi.org/10.1136/gutjnl-2016-311403 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062813712
    274 rdf:type schema:CreativeWork
    275 https://doi.org/10.1136/gutjnl-2016-311421 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026623023
    276 rdf:type schema:CreativeWork
    277 https://doi.org/10.1155/2010/170432 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018713589
    278 rdf:type schema:CreativeWork
    279 https://doi.org/10.1158/0008-5472.can-14-3051 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050762714
    280 rdf:type schema:CreativeWork
    281 https://doi.org/10.1158/0008-5472.can-15-0255 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007025850
    282 rdf:type schema:CreativeWork
    283 https://doi.org/10.1158/1078-0432.ccr-09-1438 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033591305
    284 rdf:type schema:CreativeWork
    285 https://doi.org/10.1158/1078-0432.ccr-13-2830 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023358367
    286 rdf:type schema:CreativeWork
    287 https://doi.org/10.1158/2159-8290.cd-14-0863 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029393757
    288 rdf:type schema:CreativeWork
    289 https://doi.org/10.1200/jco.2008.19.6147 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013118343
    290 rdf:type schema:CreativeWork
    291 https://doi.org/10.1200/jco.2009.26.7609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020897568
    292 rdf:type schema:CreativeWork
    293 https://doi.org/10.1200/jco.2010.30.5425 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030439270
    294 rdf:type schema:CreativeWork
    295 https://doi.org/10.1200/jco.2016.70.7547 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084826430
    296 rdf:type schema:CreativeWork
    297 https://doi.org/10.1200/po.16.00005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090382318
    298 rdf:type schema:CreativeWork
    299 https://doi.org/10.18632/oncotarget.13207 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033286470
    300 rdf:type schema:CreativeWork
    301 https://doi.org/10.5858/arpa.2015-0506-sa schema:sameAs https://app.dimensions.ai/details/publication/pub.1036718208
    302 rdf:type schema:CreativeWork
    303 https://www.grid.ac/institutes/grid.412330.7 schema:alternateName Tampere University Hospital
    304 schema:name Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    305 Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland.
    306 rdf:type schema:Organization
    307 https://www.grid.ac/institutes/grid.460356.2 schema:alternateName Central Finland Health Care District
    308 schema:name Department of Education and Research, Central Finland Central Hospital, Jyväskylä, Finland. maarit.ahtiainen@ksshp.fi.
    309 Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
    310 rdf:type schema:Organization
    311 https://www.grid.ac/institutes/grid.9681.6 schema:alternateName University of Jyväskylä
    312 schema:name Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland.
    313 Department of Education and Research, Central Finland Central Hospital, Jyväskylä, Finland.
    314 Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
    315 Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
    316 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...