Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy

Marjan M. Naeini, Felicity Newell, Lauren G. Aoude, Vanessa F. Bonazzi, Kalpana Patel, Guy Lampe, Lambros T. Koufariotis, Vanessa Lakis, Venkateswar Addala, Olga Kondrashova, Rebecca L. Johnston, Sowmya Sharma, Sandra Brosda, Oliver Holmes, Conrad Leonard, Scott Wood, Qinying Xu, Janine Thomas, Euan Walpole, G. Tao Mai, Stephen P. Ackland, Jarad Martin, Matthew Burge, Robert Finch, Christos S. Karapetis, Jenny Shannon, Louise Nott, Robert Bohmer, Kate Wilson, Elizabeth Barnes, John R. Zalcberg, B. Mark Smithers, John Simes, Timothy Price, Val Gebski, Katia Nones, David I. Watson, John V. Pearson, Andrew P. Barbour () and Nicola Waddell ()
Additional contact information
Marjan M. Naeini: QIMR Berghofer Medical Research Institute
Felicity Newell: QIMR Berghofer Medical Research Institute
Lauren G. Aoude: The University of Queensland
Vanessa F. Bonazzi: The University of Queensland
Kalpana Patel: The University of Queensland
Guy Lampe: Princess Alexandra Hospital
Lambros T. Koufariotis: QIMR Berghofer Medical Research Institute
Vanessa Lakis: QIMR Berghofer Medical Research Institute
Venkateswar Addala: QIMR Berghofer Medical Research Institute
Olga Kondrashova: QIMR Berghofer Medical Research Institute
Rebecca L. Johnston: QIMR Berghofer Medical Research Institute
Sowmya Sharma: QIMR Berghofer Medical Research Institute
Sandra Brosda: The University of Queensland
Oliver Holmes: QIMR Berghofer Medical Research Institute
Conrad Leonard: QIMR Berghofer Medical Research Institute
Scott Wood: QIMR Berghofer Medical Research Institute
Qinying Xu: QIMR Berghofer Medical Research Institute
Janine Thomas: Princess Alexandra Hospital
Euan Walpole: Princess Alexandra Hospital
G. Tao Mai: Princess Alexandra Hospital
Stephen P. Ackland: Calvary Mater Newcastle
Jarad Martin: Calvary Mater Newcastle
Matthew Burge: Royal Brisbane and Women’s Hospital
Robert Finch: Royal Brisbane and Women’s Hospital
Christos S. Karapetis: Flinders University Department of Medical Oncology, Flinders Medical Centre
Jenny Shannon: Nepean Hospital
Louise Nott: Royal Hobart Hospital
Robert Bohmer: Royal Hobart Hospital
Kate Wilson: University of Sydney
Elizabeth Barnes: University of Sydney
John R. Zalcberg: Monash University
B. Mark Smithers: Princess Alexandra Hospital
John Simes: University of Sydney
Timothy Price: The Queen Elizabeth Hospital and University of Adelaide
Val Gebski: University of Sydney
Katia Nones: QIMR Berghofer Medical Research Institute
David I. Watson: Flinders University Discipline of Surgery, Flinders Medical Centre
John V. Pearson: QIMR Berghofer Medical Research Institute
Andrew P. Barbour: The University of Queensland
Nicola Waddell: QIMR Berghofer Medical Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Oesophageal 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.

Date: 2023
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DOI: 10.1038/s41467-023-38891-x

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