IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38891-x.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    University of Queensland
    Australian Clinical Labs)

  • 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
    Mater Misericordiae)

  • 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
    University of Queensland)

  • 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
    Princess Alexandra Hospital)

  • Nicola Waddell

    (QIMR Berghofer Medical Research Institute)

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.

Suggested Citation

  • 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. John, 2023. "Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38891-x
    DOI: 10.1038/s41467-023-38891-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38891-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38891-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Xiaodun Li & Hayley E. Francies & Maria Secrier & Juliane Perner & Ahmad Miremadi & Núria Galeano-Dalmau & William J. Barendt & Laura Letchford & Genevieve M. Leyden & Emma K. Goffin & Andrew Barthorp, 2018. "Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    2. Aldo Scarpa & David K. Chang & Katia Nones & Vincenzo Corbo & Ann-Marie Patch & Peter Bailey & Rita T. Lawlor & Amber L. Johns & David K. Miller & Andrea Mafficini & Borislav Rusev & Maria Scardoni & , 2017. "Whole-genome landscape of pancreatic neuroendocrine tumours," Nature, Nature, vol. 543(7643), pages 65-71, March.
    3. Nicholas K. Hayward & James S. Wilmott & Nicola Waddell & Peter A. Johansson & Matthew A. Field & Katia Nones & Ann-Marie Patch & Hojabr Kakavand & Ludmil B. Alexandrov & Hazel Burke & Valerie Jakrot , 2017. "Whole-genome landscapes of major melanoma subtypes," Nature, Nature, vol. 545(7653), pages 175-180, May.
    4. Serena Nik-Zainal & Helen Davies & Johan Staaf & Manasa Ramakrishna & Dominik Glodzik & Xueqing Zou & Inigo Martincorena & Ludmil B. Alexandrov & Sancha Martin & David C. Wedge & Peter Van Loo & Young, 2016. "Landscape of somatic mutations in 560 breast cancer whole-genome sequences," Nature, Nature, vol. 534(7605), pages 47-54, June.
    5. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Correction: Corrigendum: Signatures of mutational processes in human cancer," Nature, Nature, vol. 502(7470), pages 258-258, October.
    6. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Signatures of mutational processes in human cancer," Nature, Nature, vol. 500(7463), pages 415-421, August.
    7. Ankur Chakravarthy & Andrew Furness & Kroopa Joshi & Ehsan Ghorani & Kirsty Ford & Matthew J. Ward & Emma V. King & Matt Lechner & Teresa Marafioti & Sergio A. Quezada & Gareth J. Thomas & Andrew Febe, 2018. "Pan-cancer deconvolution of tumour composition using DNA methylation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    8. Michael S. Lawrence & Petar Stojanov & Craig H. Mermel & James T. Robinson & Levi A. Garraway & Todd R. Golub & Matthew Meyerson & Stacey B. Gabriel & Eric S. Lander & Gad Getz, 2014. "Discovery and saturation analysis of cancer genes across 21 tumour types," Nature, Nature, vol. 505(7484), pages 495-501, January.
    9. Sarah Song & Katia Nones & David Miller & Ivon Harliwong & Karin S Kassahn & Mark Pinese & Marina Pajic & Anthony J Gill & Amber L Johns & Matthew Anderson & Oliver Holmes & Conrad Leonard & Darrin Ta, 2012. "qpure: A Tool to Estimate Tumor Cellularity from Genome-Wide Single-Nucleotide Polymorphism Profiles," PLOS ONE, Public Library of Science, vol. 7(9), pages 1-7, September.
    10. Katia Nones & Nicola Waddell & Nicci Wayte & Ann-Marie Patch & Peter Bailey & Felicity Newell & Oliver Holmes & J. Lynn Fink & Michael C. J. Quinn & Yue Hang Tang & Guy Lampe & Kelly Quek & Kelly A. L, 2014. "Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Martin Boström & Erik Larsson, 2022. "Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    2. Sebastian Carrasco Pro & Heather Hook & David Bray & Daniel Berenzy & Devlin Moyer & Meimei Yin & Adam Thomas Labadorf & Ryan Tewhey & Trevor Siggers & Juan Ignacio Fuxman Bass, 2023. "Widespread perturbation of ETS factor binding sites in cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Thomas G. Paulson & Patricia C. Galipeau & Kenji M. Oman & Carissa A. Sanchez & Mary K. Kuhner & Lucian P. Smith & Kevin Hadi & Minita Shah & Kanika Arora & Jennifer Shelton & Molly Johnson & Andre Co, 2022. "Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. A. C. Katz-Summercorn & S. Jammula & A. Frangou & I. Peneva & M. O’Donovan & M. Tripathi & S. Malhotra & M. Pietro & S. Abbas & G. Devonshire & W. Januszewicz & A. Blasko & K. Nowicki-Osuch & S. MacRa, 2022. "Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Michelle Dietzen & Haoran Zhai & Olivia Lucas & Oriol Pich & Christopher Barrington & Wei-Ting Lu & Sophia Ward & Yanping Guo & Robert E. Hynds & Simone Zaccaria & Charles Swanton & Nicholas McGranaha, 2024. "Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Ambrocio Sanchez & Pedro Ortega & Ramin Sakhtemani & Lavanya Manjunath & Sunwoo Oh & Elodie Bournique & Alexandrea Becker & Kyumin Kim & Cameron Durfee & Nuri Alpay Temiz & Xiaojiang S. Chen & Reuben , 2024. "Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Brittany N. Vandenberg & Marian F. Laughery & Cameron Cordero & Dalton Plummer & Debra Mitchell & Jordan Kreyenhagen & Fatimah Albaqshi & Alexander J. Brown & Piotr A. Mieczkowski & John J. Wyrick & S, 2023. "Contributions of replicative and translesion DNA polymerases to mutagenic bypass of canonical and atypical UV photoproducts," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. Qi Zhao & Feng Wang & Yan-Xing Chen & Shifu Chen & Yi-Chen Yao & Zhao-Lei Zeng & Teng-Jia Jiang & Ying-Nan Wang & Chen-Yi Wu & Ying Jing & You-Sheng Huang & Jing Zhang & Zi-Xian Wang & Ming-Ming He & , 2022. "Comprehensive profiling of 1015 patients’ exomes reveals genomic-clinical associations in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Ankur Chakravarthy & Ian Reddin & Stephen Henderson & Cindy Dong & Nerissa Kirkwood & Maxmilan Jeyakumar & Daniela Rothschild Rodriguez & Natalia Gonzalez Martinez & Jacqueline McDermott & Xiaoping Su, 2022. "Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Sujath Abbas & Oriol Pich & Ginny Devonshire & Shahriar A. Zamani & Annalise Katz-Summercorn & Sarah Killcoyne & Calvin Cheah & Barbara Nutzinger & Nicola Grehan & Nuria Lopez-Bigas & Rebecca C. Fitzg, 2023. "Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Peter Georgeson & Tabitha A. Harrison & Bernard J. Pope & Syed H. Zaidi & Conghui Qu & Robert S. Steinfelder & Yi Lin & Jihoon E. Joo & Khalid Mahmood & Mark Clendenning & Romy Walker & Efrat L. Amita, 2022. "Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Amanda Fitzpatrick & Marjan Iravani & Adam Mills & David Vicente & Thanussuyah Alaguthurai & Ioannis Roxanis & Nicholas C. Turner & Syed Haider & Andrew N. J. Tutt & Clare M. Isacke, 2023. "Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Jurica Levatić & Marina Salvadores & Francisco Fuster-Tormo & Fran Supek, 2022. "Mutational signatures are markers of drug sensitivity of cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    14. Kathiresan Selvam & Smitha Sivapragasam & Gregory M. K. Poon & John J. Wyrick, 2023. "Detecting recurrent passenger mutations in melanoma by targeted UV damage sequencing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    15. Se Jin Park & Gwan Woo Ku & Su Yel Lee & Daeun Kang & Wan Jin Hwang & In Beom Jeong & Sun Jung Kwon & Jaeku Kang & Ji Woong Son, 2021. "Analysis of Single Nucleotide Variants (SNVs) Induced by Exposure to PM 10 in Lung Epithelial Cells Using Whole Genome Sequencing," IJERPH, MDPI, vol. 18(3), pages 1-11, January.
    16. Heather E. Machado & Nina F. Øbro & Nicholas Williams & Shengjiang Tan & Ahmed Z. Boukerrou & Megan Davies & Miriam Belmonte & Emily Mitchell & E. Joanna Baxter & Nicole Mende & Anna Clay & Philip Anc, 2023. "Convergent somatic evolution commences in utero in a germline ribosomopathy," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    17. Xing Cheng & Jing An & Jitong Lou & Qisheng Gu & Weimin Ding & Gaith Nabil Droby & Yilin Wang & Chenghao Wang & Yanzhe Gao & Jay Ramanlal Anand & Abigail Shelton & Andrew Benson Satterlee & Breanna Ma, 2024. "Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    18. Anna Luiza Silva Almeida Vicente & Alexei Novoloaca & Vincent Cahais & Zainab Awada & Cyrille Cuenin & Natália Spitz & André Lopes Carvalho & Adriane Feijó Evangelista & Camila Souza Crovador & Rui Ma, 2022. "Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    19. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    20. Francesca Menghi & Edison T. Liu, 2022. "Functional genomics of complex cancer genomes," Nature Communications, Nature, vol. 13(1), pages 1-4, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38891-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.