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Its underlying mechanisms remain poorly understood. It is unclear whether systemic inflammation, angiogenesis, and cell\u2010to\u2010cell adhesion influence tumor budding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009132 stage I\u2013III colorectal cancer patients recruited at Huntsman Cancer Institute enrolled in the ColoCare Study. Tumor budding was evaluated using an evidence\u2010based scoring system, and patient sera were analyzed for nine circulating biomarkers using the Meso Scale Discovery platform. We examined associations between biomarkers and tumor budding using multivariable linear regression models adjusted for age, sex, neoadjuvant treatment, stage, and non\u2010steroidal anti\u2010inflammatory drug use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study population was predominantly non\u2010Hispanic White (95%), with a mean age of 61\u2009years; 56% were male. Most tumors were stage III (47%), located in the colon (64%), and exhibited low\u2010grade tumor budding (58%). Soluble intercellular adhesion molecule 1 was inversely associated with tumor budding overall (M1:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.57,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03), among females (M1:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.81,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value\u2009=\u20090.03) and later\u2010onset (\u2265\u200950\u2009years) colorectal cancer (M1:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.71,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value\u2009=\u20090.008). C\u2010reactive protein was positively associated with tumor budding in males (M1:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.23,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), while interleukin\u20108 (M1:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.96,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value\u2009=\u20090.01) and soluble vascular adhesion molecule 1 (M2:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20091.48,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value\u2009=\u20090.04) were positively associated with tumor budding in early\u2010onset patients. However, these associations did not remain statistically significant after correction for multiple testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, our findings do not provide evidence of a significant association between biomarkers of systemic inflammation, angiogenesis, and cell\u2010to\u2010cell adhesion with tumor budding count. We observed patterns for some biomarkers, yet none remained statistically significant after correction for multiple testing. These findings provide preliminary insights for future studies.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      : NCT02328677.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71267","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T10:52:05Z","timestamp":1758624725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations of Biomarkers of Systemic Inflammation, Angiogenesis, and Cell\u2010to\u2010Cell Adhesion With Tumor Budding Among Early\u2010Onset and Later\u2010Onset Colorectal Cancer Patients"],"prefix":"10.1002","volume":"14","author":[{"given":"Oda","family":"Hausmann","sequence":"first","affiliation":[{"name":"Huntsman Cancer Institute  Salt Lake City Utah USA"},{"name":"Department of Population Health Sciences University of Utah  Salt Lake City Utah USA"},{"name":"Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline P.","family":"Schobert","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute  Salt Lake City Utah USA"},{"name":"Department of Population Health Sciences University of Utah  Salt Lake City Utah USA"},{"name":"Technical University of Munich  Munich Germany"},{"name":"Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ose","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute  Salt Lake City Utah USA"},{"name":"Department of Population Health Sciences University of Utah  Salt Lake City Utah USA"},{"name":"Department of Information and Communication, Faculty for Media, Information and Design University of Applied Sciences and Arts  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Himbert","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute  Salt Lake City Utah USA"},{"name":"Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard, Medical School  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T. 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