{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:09:54Z","timestamp":1788930594808,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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>Background<\/jats:title>\n                    <jats:p>Perineural invasion (PNI) is a pathological feature associated with aggressive tumor behavior in several solid malignancies. In colorectal cancer (CRC), PNI has been reported to correlate with poorer prognosis, as well as increased risks of postoperative recurrence and metastasis. However, the available evidence regarding the prognostic significance of PNI in CRC remains limited and inconsistent. Unlike previous meta-analyses that included studies across broader time span. This study focuses on recent evidence and specifically investigates the sources of heterogeneity and its clinical significance. Therefore, this study aimed to evaluate the prognostic and clinicopathological value of PNI in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PubMed, Web of Science, Embase, and Cochrane Library databases were all thoroughly searched between January 1, 2020, and October 9, 2025.Studies included in this review comprised cohort, case\u2013control that reported on PNI status and survival outcomes in CRC. Two reviewers independently extracted the data and evaluated the studies\u2019 quality in accordance with PRISMA recommendations. The Newcastle\u2013Ottawa Scale was used to evaluate the studies\u2019 quality. By computing the hazard ratio (HR) and its 95% confidence interval (CI), the prognostic significance of PNI for CRC was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 9 retrospective studies were included. The pooled analysis suggested that PNI was associated with worse OS (HR\u00a0=\u00a02.23, 95%CI: 1.48-3.35, P &amp;lt; 0.001) and DFS (HR\u00a0=\u00a01.94, 95%CI: 1.44-2.64, P &amp;lt; 0.05) in patients with CRC. However, substantial heterogeneity was observed in both analyses (OS: I\u00b2=79.7%; DFS: I\u00b2=67.4%), and publication bias was suggested by Egger\u2019s tests (OS: p=0.0097; DFS: p=0.0085).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Based on recent studies, PNI was associated with poorer OS and DFS in CRC and may serve as a useful pathological marker for risk stratification. However, the findings should be interpreted cautiously because all included studies were retrospective and substantial heterogeneity and potential publication bias were present.<\/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\/<\/jats:ext-link>\n                      , identifier CRD420251161522.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1910736","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:40:10Z","timestamp":1788928810000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic and clinicopathological value of perineural invasion in colorectal cancer: a 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