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

M. Naeini, M.; Newell, F.; Aoude, L.G.; Bonazzi, V.F.; Patel, K.; Lampe, G.; Koufariotis, L.T.; Lakis, V.; Addala, V.; Kondrashova, O.; Johnston, R.L.; Sharma, S.; Brosda, S.; Holmes, O.; Leonard, C.; Wood, S.; Xu, Q.; Thomas, J.; Walpole, E.; Tao Mai, G.; et al.

Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/138819

Scopus	Web of Science®	Altmetric
Citations
?	?

Type:	Journal article
Title:	Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
Author:	M. Naeini, M. Newell, F. Aoude, L.G. Bonazzi, V.F. Patel, K. Lampe, G. Koufariotis, L.T. Lakis, V. Addala, V. Kondrashova, O. Johnston, R.L. Sharma, S. Brosda, S. Holmes, O. Leonard, C. Wood, S. Xu, Q. Thomas, J. Walpole, E. Tao Mai, G. et al.
Citation:	Nature Communications, 2023; 14(1)
Publisher:	Springer Science and Business Media LLC
Issue Date:	2023
ISSN:	2041-1723 2041-1723
Statement of Responsibility:	Marjan M. Naeini, Felicity Newell, LaurenG. 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
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.
Keywords:	Humans Adenocarcinoma Esophageal Neoplasms Neoadjuvant Therapy Australia Multiomics
Rights:	© The Author(s) 2023 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
DOI:	10.1038/s41467-023-38891-x
Grant ID:	http://purl.org/au-research/grants/nhmrc/2018244
Published version:	http://dx.doi.org/10.1038/s41467-023-38891-x
Appears in Collections:	Medicine publications

Files in This Item:

File	Description	Size	Format
hdl_138819.pdf	Published version	4.82 MB	Adobe PDF	View/Open

Show full item record

Adelaide Research & Scholarship