{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:19:16Z","timestamp":1787987956491,"version":"build-2784847793"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) prognosis remains challenging due to tumor heterogeneity and immune evasion driven by aberrant inflammatory signaling, and robust multicohort validated prognostic tools with clear therapeutic implications are still lacking. To address this gap, we integrated five independent CRC cohorts (TCGA, GSE17536, GSE17537, GSE29621, and GSE38832;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009931) and applied single\u2010sample gene set enrichment analysis (ssGSEA) across 15 inflammation\u2010related signaling pathways to construct a prognostic risk score model via multicohort Cox regression and LASSO\u2010Cox regression. The immune landscape was systematically characterized using immune infiltration algorithms, Cancer Immunity Cycle scoring, CellChat analysis, and single\u2010cell RNA sequencing (scRNA\u2010seq) data (GSE166555). The functional role of the candidate gene PCOLCE2 was further validated through in\u00a0vitro migration and adhesion assays, and confirmed in a syngeneic C57BL\/6 mouse subcutaneous tumor model in which MC38\u2010shPCOLCE2 cells were inoculated and treated with anti\u2010PD\u20101 antibody (200\u2009\u03bcg per mouse, every 3\u2009days) alone or in combination to evaluate the synergistic antitumor effect. The resulting 12\u2010gene inflammation\u2010related risk model achieved robust survival stratification across all five independent cohorts, with AUC values of 0.70\u20130.85 and C\u2010indices consistently outperforming existing prognostic models, demonstrating strong generalizability as a clinical prognostic tool. High\u2010risk patients exhibited significantly worse overall survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), an immunosuppressive tumor microenvironment, and elevated pro\u2010stromal remodeling signaling, patterns that were corroborated by single\u2010cell resolution analysis. Mechanistically, PCOLCE2 knockdown suppressed CRC cell migration and enhanced matrix adhesion in\u00a0vitro. Critically, in\u00a0vivo combination of PCOLCE2 knockdown with PD\u20101 blockade produced a synergistic antitumor effect superior to either monotherapy (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), highlighting PCOLCE2 as a promising therapeutic target to enhance immunotherapy response. Together, these findings present a clinically actionable, multicohort validated inflammation\u2010related prognostic model for CRC risk stratification, and position PCOLCE2 as a driver of invasion and immune evasion whose combination with PD\u20101 blockade offers a rational therapeutic strategy to improve immunotherapy efficacy in high\u2010risk CRC patients.\n                  <\/jats:p>","DOI":"10.1002\/biof.70141","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:24:56Z","timestamp":1787984696000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multicohort Construction, Immune Landscape Analysis, and\n                    <scp>PCOLCE2<\/scp>\n                    Functional Validation of an Inflammation\u2010Related Prognostic Model in Colorectal Cancer"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-3891","authenticated-orcid":false,"given":"Minjun","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-7681","authenticated-orcid":false,"given":"Wentao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology Zhujiang Hospital, Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7217-0111","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhujiang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_9_2_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_9_3_1","first-page":"145","article-title":"Colorectal Cancer Statistics, 2020","volume":"70","author":"Siegel R. 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