Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
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Published:2023-05-31
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
M. Naeini MarjanORCID, Newell FelicityORCID, Aoude Lauren G., Bonazzi Vanessa F.ORCID, Patel Kalpana, Lampe Guy, Koufariotis Lambros T., Lakis Vanessa, Addala VenkateswarORCID, Kondrashova OlgaORCID, Johnston Rebecca L.ORCID, Sharma Sowmya, Brosda SandraORCID, Holmes Oliver, Leonard ConradORCID, Wood ScottORCID, Xu Qinying, Thomas Janine, Walpole Euan, Tao Mai G., Ackland Stephen P., Martin Jarad, Burge Matthew, Finch Robert, Karapetis Christos S., Shannon Jenny, Nott LouiseORCID, Bohmer Robert, Wilson Kate, Barnes Elizabeth, Zalcberg John R., Mark Smithers B.ORCID, Simes John, Price Timothy, Gebski ValORCID, Nones KatiaORCID, Watson David I.ORCID, Pearson John V., Barbour Andrew P.ORCID, Waddell NicolaORCID
Abstract
AbstractOesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.
Funder
Department of Health | National Health and Medical Research Council PA Research Foundation
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference94 articles.
1. Collaborators, G.B.D.O.C. The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 5, 582–597 (2020). 2. Allum, W. H., Stenning, S. P., Bancewicz, J., Clark, P. I. & Langley, R. E. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J. Clin. Oncol. 27, 5062–5067 (2009). 3. van Hagen, P. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N. Engl. J. Med. 366, 2074–2084 (2012). 4. Kato, K. et al. Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: the phase 3 KEYNOTE-590 study. Ann. Oncol. 31, S1192–S1193 (2020). 5. Shah, M. A. et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study. JAMA Oncol. 5, 546–550 (2019).
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