{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:51:06Z","timestamp":1789681866723,"version":"4.0.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tumor-associated neutrophils (TANs) are abundant in the colorectal cancer (CRC) microenvironment, but their prognostic relevance remains controversial. We conducted an updated systematic review and multilevel meta-analysis to evaluate associations between TAN infiltration in primary tumors and survival outcomes in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to January 1, 2026. We included studies of histologically confirmed CRC that quantified TANs in primary tumors and reported hazard ratios (HRs) for cancer-specific survival (CSS), overall survival (OS), or disease-free survival (DFS); recurrence-free survival was combined with DFS. Multilevel random-effects models accounted for correlated effect sizes and generated overall and region-specific estimates from univariate and multivariate analyses. Prespecified subgroup analyses and multilevel meta-regression explored heterogeneity by study region, tumor stage, detection method, and TAN markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-five studies (10,356 patients) were included. High TAN infiltration was consistently associated with improved CSS (univariate HR 0.58, 95% CI 0.48\u20130.71; multivariate HR 0.66, 95% CI 0.54\u20130.81) with low heterogeneity across tumor regions. For OS and DFS, pooled estimates suggested an overall protective trend with substantial heterogeneity; subgroup analyses indicated stronger protective associations in Euro\u2013American cohorts and in stage I\u2013III disease. In contrast, multivariate DFS models suggested higher recurrence risk in Euro\u2013American populations and in studies with unclear TAN marker reporting. Meta-regression identified tumor stage and TAN markers as major contributors to heterogeneity in OS and DFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High TAN infiltration is a robust, independent favorable factor for cancer-specific survival in CRC. Associations with OS and DFS are context-dependent and appear modified by tumor stage and methodological factors, particularly TAN markers and detection methods, supporting refined prognostic stratification and further study of neutrophil-targeted strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42023493604<\/jats:ext-link>\n                      , identifier CRD42023493604.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1788605","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:34:38Z","timestamp":1771997678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Tumor-associated neutrophils and survival outcomes in colorectal cancer: a systematic review and multilevel meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Ran","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, 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