Nature Communications (May 2023)
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,
- Nicola Waddell
Affiliations
- Marjan M. Naeini
- QIMR Berghofer Medical Research Institute
- Felicity Newell
- QIMR Berghofer Medical Research Institute
- Lauren G. Aoude
- Frazer Institute, The University of Queensland
- Vanessa F. Bonazzi
- Frazer Institute, The University of Queensland
- Kalpana Patel
- Frazer Institute, 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
- Frazer Institute, 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
- Department of Medical Oncology, Calvary Mater Newcastle
- Jarad Martin
- Department of Radiation Oncology, 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 Cancer Care Centre, Nepean Hospital
- Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital
- Robert Bohmer
- Department of General Surgery, Royal Hobart Hospital
- Kate Wilson
- NHMRC Clinical Trials Centre, University of Sydney
- Elizabeth Barnes
- NHMRC Clinical Trials Centre, University of Sydney
- John R. Zalcberg
- Department of Epidemiology and Preventive Medicine, Monash University
- B. Mark Smithers
- Princess Alexandra Hospital
- John Simes
- NHMRC Clinical Trials Centre, University of Sydney
- Timothy Price
- Medical Oncology Unit, The Queen Elizabeth Hospital and University of Adelaide
- Val Gebski
- NHMRC Clinical Trials Centre, 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
- Frazer Institute, The University of Queensland
- Nicola Waddell
- QIMR Berghofer Medical Research Institute
- DOI
- https://doi.org/10.1038/s41467-023-38891-x
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.
