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

doi:10.1038/s41467-023-38891-x

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

Nat Commun. 2023 May 31;14(1):3155. doi: 10.1038/s41467-023-38891-x.

Authors

Marjan M Naeini¹, Felicity Newell¹, Lauren G Aoude², Vanessa F Bonazzi², Kalpana Patel², Guy Lampe³, Lambros T Koufariotis¹, Vanessa Lakis¹, Venkateswar Addala¹, Olga Kondrashova¹, Rebecca L Johnston¹, Sowmya Sharma^{1

4

5}, Sandra Brosda², Oliver Holmes¹, Conrad Leonard¹, Scott Wood¹, Qinying Xu¹, Janine Thomas^{3

6}, Euan Walpole³, G Tao Mai³, Stephen P Ackland⁷, Jarad Martin⁸, Matthew Burge⁹, Robert Finch⁹, Christos S Karapetis¹⁰, Jenny Shannon¹¹, Louise Nott¹², Robert Bohmer¹³, Kate Wilson¹⁴, Elizabeth Barnes¹⁴, John R Zalcberg¹⁵, B Mark Smithers^{3

4}, John Simes¹⁴, Timothy Price¹⁶, Val Gebski¹⁴, Katia Nones¹, David I Watson¹⁷, John V Pearson¹, Andrew P Barbour^#^{18

19}, Nicola Waddell^#²⁰

Affiliations

¹ QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
² Frazer Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia.
³ Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia.
⁴ Faculty of Medicine, University of Queensland, Brisbane, QLD, 4006, Australia.
⁵ Anatomical Pathology, Australian Clinical Labs, 2153, Sydney, Australia.
⁶ Mater Research Institute, Mater Misericordiae, South Brisbane, QLD, 4101, Australia.
⁷ Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, 2298, Australia.
⁸ Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, 2298, Australia.
⁹ Royal Brisbane and Women's Hospital, Herston, QLD, 4029, Australia.
¹⁰ Flinders University Department of Medical Oncology, Flinders Medical Centre, Adelaide, SA, 5042, Australia.
¹¹ Nepean Cancer Care Centre, Nepean Hospital, Sydney, NSW, 2747, Australia.
¹² Department of Medical Oncology, Royal Hobart Hospital, Hobart, TAS, Australia.
¹³ Department of General Surgery, Royal Hobart Hospital, Hobart, TAS, Australia.
¹⁴ NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2006, Australia.
¹⁵ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.
¹⁶ Medical Oncology Unit, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, 5011, Australia.
¹⁷ Flinders University Discipline of Surgery, Flinders Medical Centre, Adelaide, SA, 5042, Australia.
¹⁸ Frazer Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia. [email protected].
¹⁹ Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia. [email protected].
²⁰ QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / drug therapy
Adenocarcinoma* / genetics
Australia
Esophageal Neoplasms* / drug therapy
Esophageal Neoplasms* / genetics
Humans
Multiomics
Neoadjuvant Therapy

Supplementary concepts

Adenocarcinoma Of Esophagus