eprintid: 10144179 rev_number: 6 eprint_status: archive userid: 699 dir: disk0/10/14/41/79 datestamp: 2022-02-24 07:59:23 lastmod: 2022-02-24 07:59:23 status_changed: 2022-02-24 07:59:23 type: article metadata_visibility: show sword_depositor: 699 creators_name: Silva, Arnaldo NS creators_name: Saito, Yuichi creators_name: Yoshikawa, Takaki creators_name: Oshima, Takashi creators_name: Hayden, Jeremy D creators_name: Oosting, Jan creators_name: Earle, Sophie creators_name: Hewitt, Lindsay C creators_name: Slaney, Hayley L creators_name: Wright, Alex creators_name: Inam, Imran creators_name: Langley, Ruth E creators_name: Allum, William creators_name: Nankivell, Matthew G creators_name: Hutchins, Gordon creators_name: Cunningham, David creators_name: Grabsch, Heike I title: Increasing frequency of gene copy number aberrations is associated with immunosuppression and predicts poor prognosis in gastric adenocarcinoma ispublished: inpress divisions: UCL divisions: J38 divisions: D65 divisions: B02 note: © The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com abstract: BACKGROUND: Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. METHODS: Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. RESULTS: The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. CONCLUSION: CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions. date: 2022-02-18 date_type: published publisher: Oxford University Press (OUP) official_url: https://doi.org/10.1093/bjs/znab460 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1940411 doi: 10.1093/bjs/znab460 medium: Print-Electronic pii: 6530562 lyricists_name: Langley, Ruth lyricists_name: Nankivell, Matthew lyricists_id: RELAN40 lyricists_id: MNANK23 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner funding_acknowledgements: [Cancer Research UK]; [Yorkshire Cancer Research]; [Pathological Society of Great Britain and Ireland]; [Academy of Medical Sciences]; [Sasakawa Cancer Foundation]; [Association of Clinical Pathologists] full_text_status: public publication: British Journal of Surgery article_number: znab460 event_location: England issn: 0007-1323 citation: Silva, Arnaldo NS; Saito, Yuichi; Yoshikawa, Takaki; Oshima, Takashi; Hayden, Jeremy D; Oosting, Jan; Earle, Sophie; ... Grabsch, Heike I; + view all <#> Silva, Arnaldo NS; Saito, Yuichi; Yoshikawa, Takaki; Oshima, Takashi; Hayden, Jeremy D; Oosting, Jan; Earle, Sophie; Hewitt, Lindsay C; Slaney, Hayley L; Wright, Alex; Inam, Imran; Langley, Ruth E; Allum, William; Nankivell, Matthew G; Hutchins, Gordon; Cunningham, David; Grabsch, Heike I; - view fewer <#> (2022) Increasing frequency of gene copy number aberrations is associated with immunosuppression and predicts poor prognosis in gastric adenocarcinoma. British Journal of Surgery , Article znab460. 10.1093/bjs/znab460 <https://doi.org/10.1093/bjs%2Fznab460>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10144179/1/znab460.pdf