{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:55:33Z","timestamp":1791608133362,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CXCL8 is an inflammatory chemokine elevated in the colorectal cancer (CRC) tumour microenvironment. CXCR2, the major receptor for CXCL8, is predominantly expressed by neutrophils. In the cancer setting, CXCL8 plays important roles in neutrophil chemotaxis, facilitating angiogenesis, invasion, and metastasis. This study aimed to assess the spatial distribution of <jats:italic>CXCL8<\/jats:italic> mRNA expression in CRC specimens, explore associations with clinical characteristics, and investigate the underlying biology of aberrant <jats:italic>CXCL8<\/jats:italic> levels. CXCR2 expression was also assessed in a second cohort of unique CRC primary tumours and synchronously resected matched liver metastases. A previously constructed tissue microarray consisting of a cohort of stage I\u2013IV CRC patients undergoing surgical resection with curative intent (<jats:italic>n<\/jats:italic>\u00a0=\u2009438) was probed for <jats:italic>CXCL8<\/jats:italic> via RNAscope\u00ae. Analysis was performed using HALO\u00ae digital pathology software to quantify expression in the tumour and stromal compartments. Scores were assessed for association with clinical characteristics. Mutational analyses were performed on a subset of these patients to determine genomic differences in patients with high <jats:italic>CXCL8<\/jats:italic> expression. A second cohort of stage IV CRC patients with primary and matched metastatic liver tumours was stained via immunohistochemistry for CXCR2, and scores were assessed for clinical significance. <jats:italic>CXCL8<\/jats:italic> expression within the stromal compartment was associated with reduced cancer\u2010specific survival in the first cohort (<jats:italic>p<\/jats:italic>\u00a0=\u20090.035), and this relationship was potentiated in right\u2010sided colon cancer cases (<jats:italic>p<\/jats:italic>\u00a0=\u20090.009). High <jats:italic>CXCL8<\/jats:italic> within the stroma was associated with driving a more stromal\u2010rich phenotype and the presence of metastases. When stromal <jats:italic>CXCL8<\/jats:italic> scores were combined with tumour\u2010infiltrating macrophage counts or systemic neutrophil counts, patients classified as high for both markers had significantly poorer prognosis. CXCR2+ immune cell infiltration was associated with increased stromal invasion in liver metastases (<jats:italic>p<\/jats:italic>\u00a0=\u20090.037). These data indicate a role for <jats:italic>CXCL8<\/jats:italic> in driving unfavourable tumour histological features and promoting metastases. This study suggests that inhibiting <jats:italic>CXCL8<\/jats:italic>\/CXCR2 should be investigated in patients with right\u2010sided colonic disease and stroma\u2010rich tumours.<\/jats:p>","DOI":"10.1002\/cjp2.290","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T23:05:10Z","timestamp":1658790310000},"page":"509-520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<scp>CXCL8<\/scp> expression is associated with advanced stage, right sidedness, and distinct histological features of colorectal cancer"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-1331","authenticated-orcid":false,"given":"Kathryn AF","family":"Pennel","sequence":"first","affiliation":[{"name":"Wolfson Wohl Cancer Research Institute, Institute of Cancer Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean 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of Cancer Sciences University of Glasgow  Glasgow UK"},{"name":"Department of Surgery University of Glasgow, Glasgow Royal Infirmary  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"Rebus","sequence":"additional","affiliation":[{"name":"Wolfson Wohl Cancer Research Institute, Institute of Cancer Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"GPOL Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hay","sequence":"additional","affiliation":[{"name":"Glasgow Tissue Research Facility Queen Elizabeth University Hospital  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noori N","family":"Maka","sequence":"additional","affiliation":[{"name":"Department of Pathology Queen Elizabeth University Hospital  Glasgow 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