{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:41Z","timestamp":1787027801386,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","award":["NR11-LABX"],"award-info":[{"award-number":["NR11-LABX"]}]},{"name":"Laboratoire d\u2019Excellence Toulouse Cancer (TOUCAN)","award":["NR11-LABX"],"award-info":[{"award-number":["NR11-LABX"]}]},{"name":"CALYM\/Institute Carnot","award":["NR11-LABX"],"award-info":[{"award-number":["NR11-LABX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r\/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r\/r patients who may benefit from new therapeutic strategies. This study aimed to evaluate the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients including 30 r\/r cHL after first-line chemotherapy. Gene expression profiling (GEP) using NanoString technology identified a 19-gene immune signature at diagnosis predictive of cHL relapse, but dependent on histological subtypes. Genes related to tumor survival were found upregulated while genes related to B-lineage were downregulated at diagnosis in r\/r nodular sclerosis cHL. In contrast to the mixed-cellularity subtype, comparative GEP analyses between paired diagnosis\/relapse biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, supporting an immune contexture switch at relapse with upregulation of immunosuppressive cytokines, such as LGALS1 and TGFB1, and downregulation of the T-cell co-stimulatory receptor ICOS. These results indicate that the predictive value of immune signature in cHL is strongly influenced by histological subtype which should be considered when assessing new immunotherapy target strategies.<\/jats:p>","DOI":"10.3390\/cancers14194893","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:07:43Z","timestamp":1665187663000},"page":"4893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Claire","family":"Lamaison","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire de Rennes, P\u00f4le Biologie, 35033 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2193-4104","authenticated-orcid":false,"given":"Juliette","family":"Ferrant","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Rennes, P\u00f4le Biologie, 35033 Rennes, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, INSERM, Unit\u00e9 Mixte de Recherche U1236, Universit\u00e9 Rennes 1, \u00c9tablissement Fran\u00e7ais du Sang Bretagne, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Gravelle","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, France"},{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, INSERM, U1037, 31037 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence TOUCAN, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Traverse-Glehen","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomopathologie, Centre Hospitalier Universitaire de Lyon-Sud, 69495 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Ghesqui\u00e8res","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie, Centre Hospitalier Universitaire de Lyon-Sud, Universit\u00e9 Claude Bernard Lyon-1, Pierre-B\u00e9nite, 69495 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Tosolini","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, INSERM, U1037, 31037 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence TOUCAN, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Rossi","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie, Centre Hospitalier Universitaire Dijon, H\u00f4pital Fran\u00e7ois Mitterrand, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loic","family":"Ysebaert","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, INSERM, U1037, 31037 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence TOUCAN, 31037 Toulouse, France"},{"name":"Service d\u2019H\u00e9matologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, France"},{"name":"Universit\u00e9 de Toulouse III Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Brousset","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, France"},{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, INSERM, U1037, 31037 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence TOUCAN, 31037 Toulouse, France"},{"name":"Universit\u00e9 de Toulouse III Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5375-7512","authenticated-orcid":false,"given":"Camille","family":"Laurent","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, France"},{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, INSERM, U1037, 31037 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence TOUCAN, 31037 Toulouse, France"},{"name":"Universit\u00e9 de Toulouse III Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3201-6109","authenticated-orcid":false,"given":"Charlotte","family":"Syrykh","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, France"},{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, INSERM, U1037, 31037 Toulouse, France"},{"name":"Universit\u00e9 de Toulouse III Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1182\/blood.V97.2.496","article-title":"Down-Regulation of BOB.1\/OBF.1 and Oct2 in Classical Hodgkin Disease but Not in Lymphocyte Predominant Hodgkin Disease Correlates with Immunoglobulin Transcription","volume":"97","author":"Stein","year":"2001","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 Revision of the World Health Organization Classification of Lymphoid Neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3816\/CLM.2009.n.042","article-title":"Hodgkin Lymphoma: An Update on Its Biology with New Insights into Classification","volume":"9","author":"Mani","year":"2009","journal-title":"Clin. Lymphoma Myeloma"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1136\/jcp.55.3.162","article-title":"Hodgkin\u2019s Lymphoma: The Pathologist\u2019s Viewpoint","volume":"55","author":"Pileri","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4103\/0971-5851.177038","article-title":"Hodgkin Lymphoma: A Clinicopathological and Immunophenotypic Study","volume":"37","author":"Konkay","year":"2016","journal-title":"Indian J. Med. Paediatr. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1182\/blood-2012-06-439570","article-title":"Gene Expression Profiling of Microdissected Hodgkin Reed-Sternberg Cells Correlates with Treatment Outcome in Classical Hodgkin Lymphoma","volume":"120","author":"Steidl","year":"2012","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000321567","article-title":"Refined Prognostic Role of CD68-Positive Tumor Macrophages in the Context of the Cellular Micromilieu of Classical Hodgkin Lymphoma","volume":"77","author":"Tzankov","year":"2010","journal-title":"Pathobiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3109\/10428194.2012.698274","article-title":"Macrophage, Mast Cell and T Lymphocyte Infiltrations Are Independent Predictive Biomarkers of Primary Refractoriness or Early Relapse in Classical Hodgkin Lymphoma","volume":"54","author":"Deau","year":"2013","journal-title":"Leuk. Lymphoma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3109\/10428194.2014.917636","article-title":"CD68-Positive Tumor-Associated Macrophages Predict Unfavorable Treatment Outcomes in Classical Hodgkin Lymphoma in Correlation with Interim Fluorodeoxyglucose-Positron Emission Tomography Assessment","volume":"56","author":"Touati","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1016\/j.ejca.2013.05.024","article-title":"The Prognostic Impact of Tumour-Associated Macrophages and Reed-Sternberg Cells in Paediatric Hodgkin Lymphoma","volume":"49","author":"Gupta","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/hon.2249","article-title":"Evaluation of the Prognostic Role of Tumour-Associated Macrophages in Newly Diagnosed Classical Hodgkin Lymphoma and Correlation with Early FDG-PET Assessment","volume":"35","author":"Cencini","year":"2017","journal-title":"Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/hon.878","article-title":"Prognostic Impact of Tumour-Infiltrating Th2 and Regulatory T Cells in Classical Hodgkin Lymphoma","volume":"27","author":"Schreck","year":"2009","journal-title":"Hematol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3324\/haematol.2010.031542","article-title":"Tumor-Infiltrating Macrophages Correlate with Adverse Prognosis and Epstein-Barr Virus Status in Classical Hodgkin\u2019s Lymphoma","volume":"96","author":"Kamper","year":"2011","journal-title":"Haematologica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1200\/JCO.2012.43.4589","article-title":"Gene Expression-Based Model Using Formalin-Fixed Paraffin-Embedded Biopsies Predicts Overall Survival in Advanced-Stage Classical Hodgkin Lymphoma","volume":"31","author":"Scott","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41375-021-01314-1","article-title":"Gene Expression-Based Outcome Prediction in Advanced Stage Classical Hodgkin Lymphoma Treated with BEACOPP","volume":"35","author":"Jachimowicz","year":"2021","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1182\/blood-2005-12-5125","article-title":"Tumor Microenvironment and Mitotic Checkpoint Are Key Factors in the Outcome of Classic Hodgkin Lymphoma","volume":"108","author":"Morente","year":"2006","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rancea, M., Monsef, I., von Tresckow, B., Engert, A., and Skoetz, N. (2013). High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Patients with Relapsed\/Refractory Hodgkin Lymphoma. Cochrane Database Syst. Rev., 6.","DOI":"10.1002\/14651858.CD009411.pub2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.bbmt.2006.06.006","article-title":"Long-Term Results of Autologous Stem Cell Transplantation for Primary Refractory or Relapsed Hodgkin\u2019s Lymphoma","volume":"12","author":"Majhail","year":"2006","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1097\/HS9.0000000000000020","article-title":"Immune Checkpoint Inhibition in Hodgkin Lymphoma","volume":"2","author":"Moy","year":"2018","journal-title":"Hemasphere"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1200\/JCO.2017.72.7925","article-title":"Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma","volume":"35","author":"Chan","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12308-019-00350-2","article-title":"Therapeutic Targets and Microenvironment in Sequential Biopsies of Classical Hodgkin Lymphoma at Diagnosis and Relapse","volume":"12","author":"Schnitter","year":"2019","journal-title":"J. Hematopathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1056\/NEJMoa0905680","article-title":"Tumor-Associated Macrophages and Survival in Classic Hodgkin\u2019s Lymphoma","volume":"362","author":"Steidl","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1182\/blood-2008-07-168096","article-title":"Molecular Profiling of Classical Hodgkin Lymphoma Tissues Uncovers Variations in the Tumor Microenvironment and Correlations with EBV Infection and Outcome","volume":"113","author":"Chetaille","year":"2009","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1200\/JCO.2011.39.9881","article-title":"Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome","volume":"31","author":"Greaves","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1084\/jem.184.4.1495","article-title":"Hodgkin and Reed-Sternberg Cells in Hodgkin\u2019s Disease Represent the Outgrowth of a Dominant Tumor Clone Derived from (Crippled) Germinal Center B Cells","volume":"184","author":"Kanzler","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood-2010-03-275305","article-title":"CAL-101, a P110delta Selective Phosphatidylinositol-3-Kinase Inhibitor for the Treatment of B-Cell Malignancies, Inhibits PI3K Signaling and Cellular Viability","volume":"117","author":"Lannutti","year":"2011","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1182\/blood-2016-02-700773","article-title":"Pharmacological Restoration and Therapeutic Targeting of the B-Cell Phenotype in Classical Hodgkin Lymphoma","volume":"129","author":"Du","year":"2017","journal-title":"Blood"},{"key":"ref_28","first-page":"1381","article-title":"Prognostic Significance of CD20 Expression in Classical Hodgkin Lymphoma: A Clinicopathological Study of 119 Cases","volume":"9","author":"Tzankov","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Abuelgasim, K.A., Shammari, R.A., Alshieban, S., Alahmari, B., Alzahrani, M., Alhejazi, A., Alaskar, A., and Damlaj, M. (2021). Impact of Cluster of Differentiation 20 Expression and Rituximab Therapy in Classical Hodgkin Lymphoma: Real World Experience. Leuk. Res. Rep., 15.","DOI":"10.1016\/j.lrr.2021.100240"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3960\/jslrt.20010","article-title":"Clinicopathological Significance of CD79a Expression in Classic Hodgkin Lymphoma","volume":"60","author":"Sakatani","year":"2020","journal-title":"J. Clin. Exp. Hematop."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1182\/blood.V97.4.1063","article-title":"Expression of the C-Met Proto-Oncogene and Its Ligand, Hepatocyte Growth Factor, in Hodgkin Disease","volume":"97","author":"Teofili","year":"2001","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/leu.2014.345","article-title":"The IL-15 Cytokine System Provides Growth and Survival Signals in Hodgkin Lymphoma and Enhances the Inflammatory Phenotype of HRS Cells","volume":"29","author":"Ullrich","year":"2015","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1182\/blood.V98.9.2784","article-title":"Functional Expression of Receptor Activator of Nuclear Factor \u039aB in Hodgkin Disease Cell Lines","volume":"98","author":"Fiumara","year":"2001","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.yexcr.2010.12.017","article-title":"CXCR3 in T Cell Function","volume":"317","author":"Groom","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1182\/blood-2013-06-508044","article-title":"Defining Characteristics of Classical Hodgkin Lymphoma Microenvironment T-Helper Cells","volume":"122","author":"Greaves","year":"2013","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Brune, M.M., Juskevicius, D., Haslbauer, J., Dirnhofer, S., and Tzankov, A. (2021). Genomic Landscape of Hodgkin Lymphoma. Cancers, 13.","DOI":"10.3390\/cancers13040682"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1158\/2326-6066.CIR-16-0201","article-title":"Classical Hodgkin Lymphoma with Reduced \u03922M\/MHC Class I Expression Is Associated with Inferior Outcome Independent of 9p24.1 Status","volume":"4","author":"Roemer","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_38","first-page":"1209","article-title":"Immunohistochemical Evidence of a Role for Transforming Growth Factor Beta in the Pathogenesis of Nodular Sclerosing Hodgkin\u2019s Disease","volume":"136","author":"Kadin","year":"1990","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1411087","article-title":"PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin\u2019s Lymphoma","volume":"372","author":"Ansell","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/s41375-021-01421-z","article-title":"Reverted Exhaustion Phenotype of Circulating Lymphocytes as Immune Correlate of Anti-PD1 First-Line Treatment in Hodgkin Lymphoma","volume":"36","author":"Thelen","year":"2022","journal-title":"Leukemia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1001\/jamaoncol.2020.0750","article-title":"Efficacy of Nivolumab and AVD in Early-Stage Unfavorable Classic Hodgkin Lymphoma: The Randomized Phase 2 German Hodgkin Study Group NIVAHL Trial","volume":"6","author":"Goergen","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1182\/blood.2020008553","article-title":"Tumor and Microenvironment Response but No Cytotoxic T-Cell Activation in Classic Hodgkin Lymphoma Treated with Anti-PD1","volume":"136","author":"Reinke","year":"2020","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Oelmann, E., Stein, H., Berdel, W.E., and Herbst, H. (2015). Expression of Interleukin-1 and Interleukin-1 Receptors Type 1 and Type 2 in Hodgkin Lymphoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138747"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1182\/blood-2007-08-105643","article-title":"IL-21 Is Expressed in Hodgkin Lymphoma and Activates STAT5: Evidence That Activated STAT5 Is Required for Hodgkin Lymphomagenesis","volume":"111","author":"Scheeren","year":"2008","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/19\/4893\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:21Z","timestamp":1760143641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/19\/4893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":44,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cancers14194893"],"URL":"https:\/\/doi.org\/10.3390\/cancers14194893","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]}}}