Silva, Arnaldo NS;
Saito, Yuichi;
Yoshikawa, Takaki;
Oshima, Takashi;
Hayden, Jeremy D;
Oosting, Jan;
Earle, Sophie;
... Grabsch, Heike I; + view all
(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.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Increasing frequency of gene copy number aberrations is associated with immunosuppression and predicts poor prognosis in gastric adenocarcinoma |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/bjs/znab460 |
| Publisher version: | https://doi.org/10.1093/bjs/znab460 |
| Language: | English |
| Additional information: | © 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 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10144179 |
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