{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:10:42Z","timestamp":1790334642652,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012538","name":"Swedish Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017\u201000675"],"award-info":[{"award-number":["2017\u201000675"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016756","name":"Kempe Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Twenty\u2010five percent of colon cancer patients having curative surgery will recur. Most of them will die from distant metastasis partly due to shortcomings of routine histopathological analysis, that is, undetected tumor cells in the regional lymph node field. We have developed ColoNode, an mRNA test in which five biomarkers are quantified and related to a house\u2010keeping gene. Thereby, four different risk groups are defined from low to very high\u2010risk of recurrence being highly valuable as various indicators of the risk of occult tumor cell dissemination and their aggressiveness. Here we report results of the 5\u2010year survival analysis of a prospective study involving nine Swedish hospitals comparing ColoNode with routine histopathology. The study involves 186 colon cancer patients. The following four conclusions can be drawn: (1) ColoNode surpassed histopathology by identifying all 20 patients who were found by histopathology and an additional seven patients who recurred. Multivariate analysis provided a hazard ratio of 6.7 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002) while histopathology lost its significance (HR: 1.3;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.60). Only perineural invasion remained as an independent risk factor apart from ColoNode, with a hazard ratio of 2.7 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.038). (2) Patients belonging to medium\u2010risk group apparently benefited from adjuvant chemotherapy treatment. (3) A total of 113 patients (\u224860%) belonged to the low\u2010risk group and can be considered cured by surgery alone. (4) Four patients were missed by both ColoNode and histopathology. Possible reasons for this are discussed. The results suggest that the ColoNode test should be added to the arsenal of prognostic tools, maybe even replacing histopathological lymph node analysis.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70743","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:48:37Z","timestamp":1790333317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improved Prediction of Colon Cancer Recurrence Using the\n                    <scp>ColoNode mRNA<\/scp>\n                    Test: A 5\u2010Year Survival Analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-4798","authenticated-orcid":false,"given":"Basel","family":"Sitohy","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Department of Diagnostics and Intervention, Oncology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Lindmark","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University  Helsingborg Sweden"},{"name":"Specialistl\u00e4karna  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Israelsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Olsson","sequence":"additional","affiliation":[{"name":"HiloProbe AB  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Roshdy","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Department of Diagnostics and Intervention, Oncology Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Department of Molecular Biology, Faculty of Biotechnology University of Sadat City  Sadat City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Blomqvist","sequence":"additional","affiliation":[{"name":"HiloProbe AB  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Kero","sequence":"additional","affiliation":[{"name":"HiloProbe AB  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"S\u00f6derholm","sequence":"additional","affiliation":[{"name":"Department of Surgery Blekinge Hospital  Karlskrona Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Turi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Cytology Blekinge Hospital  Karlskrona Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorbj\u00f6rn","family":"Sakari","sequence":"additional","affiliation":[{"name":"Department of Surgery, CFUG G\u00e4vle Hospital  G\u00e4vle Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Dooper","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Cytology G\u00e4vle Hospital  G\u00e4vle Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dafnis","sequence":"additional","affiliation":[{"name":"Colorectal Unit, Department of Surgery and Urology M\u00e4larsjukhuset  Eskilstuna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pehr","family":"Forsberg","sequence":"additional","affiliation":[{"name":"Unilabs, Clinical Pathology and Cytology M\u00e4larsjukhuset  Eskilstuna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Skovsted","sequence":"additional","affiliation":[{"name":"Unit for Surgery \u00d6rnsk\u00f6ldsvik Hospital  \u00d6rnsk\u00f6ldsvik Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Walld\u00e9n","sequence":"additional","affiliation":[{"name":"Centrum for Surgery Sundsvall Hospital  Sundsvall Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Han","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Intervention, Surgery Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Department of Surgery Skellefte\u00e5 Hospital  Skellefte\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ruteg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Intervention, Surgery Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Nordmyr","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology Link\u00f6ping University Hospital  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e5ns","family":"Muhrbeck","sequence":"additional","affiliation":[{"name":"Department of Surgery Vrinnevi Hospital  Norrk\u00f6ping Sweden"},{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-4423","authenticated-orcid":false,"given":"Marie\u2010Louise","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"J.Ferlay M.Ervik F.Lam et\u00a0al. \u201cGlobal Cancer Observatory: Cancer Today February 2024 \u201dhttps:\/\/gco.iarc.who.int\/today."},{"key":"e_1_2_12_3_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung H.","year":"2021","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"e_1_2_12_4_1","first-page":"43","article-title":"Cancer 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Lymph Nodes in Stage I\u2013III Colorectal Cancer Patients: A Retrospective Single Institution Cohort Study of 1167 Consecutive Patients","volume":"16","author":"Tsai H. L.","year":"2016","journal-title":"BMC Surgery"},{"key":"e_1_2_12_8_1","unstructured":"M. B.Loughrey P.Quirke andN. A.Shepherd \u201cStandards and Datasets for Reporting Cancers. Dataset for Histopathological Reporting of Colorectal Cancer \u201dVersion 5 April 2023 reviewed 2026. The Royal College of Pathologists. 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M.","year":"2021","journal-title":"Diseases of the Colon and Rectum"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/bjc.2012.220","article-title":"Lymph Node Tissue Kallikrein\u2010Related Peptidase 6 mRNA\u2014A Progression Marker for Colorectal Cancer","volume":"107","author":"Ohlsson L.","year":"2012","journal-title":"British Journal of Cancer"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1006\/scbi.1998.0119","article-title":"The Carcinoembryonic Antigen (CEA) Family: Structures, Suggested Functions and Expression in Normal and Malignant Tissues","volume":"9","author":"Hammarstr\u00f6m S.","year":"1999","journal-title":"Seminars in Cancer Biology"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/sj.bjc.6603206","article-title":"Biomarker Selection for Detection of Occult Tumour Cells in Lymph Nodes of Colorectal Cancer Patients Using Real\u2010Time Quantitative RT\u2010PCR","volume":"95","author":"Ohlsson L.","year":"2006","journal-title":"British Journal of Cancer"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1002\/ijc.26182","article-title":"Lymph Node CEA and MUC2 mRNA as Useful Predictors of Outcome in Colorectal Cancer","volume":"130","author":"Ohlsson L.","year":"2012","journal-title":"International Journal of Cancer"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2217\/bmm-2019-0203","article-title":"Biomarker mRNAs as Prognostic Tools for Lymph Node Analysis in Colorectal Cancer","volume":"13","author":"Hammarstr\u00f6m S.","year":"2019","journal-title":"Biomarkers in Medicine"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/ijc.34718","article-title":"qRT\u2010PCR Analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in Colon Cancer Lymph Nodes\u2014An Improved Method for Assessment of Tumor Stage and Prognosis","volume":"154","author":"Lindmark G.","year":"2024","journal-title":"International Journal of Cancer"},{"key":"e_1_2_12_17_1","unstructured":"R.Palmqvist C.Miklos \u00c5.Fred H.Nobin Gustafsson andJ.Sahibzada \u201cKolon och rektum\u2014Tum\u00f6rer och tum\u00f6rlika f\u00f6r\u00e4ndringar \u201dDocument Name: KVAST\u2010CRC\u20102022 accessed 2022 https:\/\/medlem.foreningssupport.se\/foreningar\/uploads\/L15178\/kvast\/gastro\/KVAST\u2010CRC\u20102022.pdf."},{"key":"e_1_2_12_18_1","unstructured":"M. B.Loughrey P.Quirke andN. A.Shepherd Dataset for Histopathological Reporting of Colorectal CancerDocument Number G049 in: Standards and Datasets for Reporting Cancers. 4th edition accessed 2018 www.rcpath.org\/uploads\/assets\/c8b61ba0\u2010ae3f\u201043f1\u201085ffd3ab9f17cfe6\/G049\u2010Dataset\u2010for\u2010histopathological\u2010reporting\u2010of\u2010colorectal\u2010cancer."},{"key":"e_1_2_12_19_1","unstructured":"Regional Cancer Centra (RCC) Knowledge Bank (cancercentrum.se) \u201cNational Health Care Program for Colon and Rectal Cancer Version\u201dVersion 1.0 assessed February 2 2016 and version 3.1 accessed February 2 2023 https:\/\/kunskapsbanken.cancercentrum.se\/diagnoser\/tjock\u2010och\u2010andtarmscancer\/vardprogram.pdf."},{"key":"e_1_2_12_20_1","first-page":"1","volume-title":"Evaluation of Methods in Health Care: A Handbook. Appendix\u00a010. Statistical Concepts in Medical Evaluations","author":"SBU","year":"2014"},{"key":"e_1_2_12_21_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12113308","article-title":"Recurrence Risk After Radical Colorectal Cancer Surgery\u2010Less Than Before, but How High Is It?","volume":"12","author":"Osterman E.","year":"2020","journal-title":"Cancers"},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1589533","article-title":"High IL\u201010 mRNA Levels in Regional Lymph Nodes of Colon Cancer Patients Indicate Poor Prognosis","volume":"16","author":"Mohamed A.","year":"2025","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_12_23_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2025.1628069","article-title":"Combined Serine Protease PRSS22 and CEA mRNA Analysis Identifies the Majority of Colon Cancer Patients That Recur Within 12\u2009Years","volume":"15","author":"Mohamed A.","year":"2025","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_12_24_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.766653","article-title":"Nerve Dependence In Colorectal Cancer","volume":"10","author":"Zhang L.","year":"2022","journal-title":"Frontiers in Cell and Development Biology"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13402-023-00857-y","article-title":"Perineural Invasion in Colorectal Cancer: Mechanisms of Action and Clinical Relevance","volume":"47","author":"Wang H.","year":"2024","journal-title":"Cellular Oncology"},{"key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/j.0300-9475.2004.01440.x","article-title":"Utility of the Housekeeping Genes 18S rRNA, \u03b2\u2010Actin and Glyceraldehyde\u20103\u2010Phosphate\u2010Dehydrogenase (GAPDH) for Normalization in Real\u2010Time Quantitative RT\u2010PCR Analysis of Gene Expression in Human T Lymphocytes","volume":"59","author":"Bas A.","year":"2004","journal-title":"Scandinavian Journal of Immunology"},{"key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1046\/j.1365-2249.2003.02035.x","article-title":"Increased Expression of Antimicrobial Peptides and Lysozyme in Colonic Epithelial Cells of Patients With Ulcerative Colitis","volume":"131","author":"Fahlgren A.","year":"2003","journal-title":"Clinical and Experimental Immunology"},{"key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/ijc.35442","article-title":"Utility of Circulating Tumor DNA to Detect Minimal Residual Disease in Colorectal Cancer: A Systematic Review and Network Meta\u2010Analysis","volume":"157","author":"Hoang T.","year":"2025","journal-title":"International Journal of Cancer"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70743","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70743","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70743","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:48:42Z","timestamp":1790333322000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":27,"alternative-id":["10.1002\/ijc.70743"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70743","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"2026-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ijc.70743"}}