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Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial

Author

Listed:
  • Jennifer J. Knox

    (University Health Network)

  • Gun Ho Jang

    (Ontario Institute for Cancer Research)

  • Robert C. Grant

    (University Health Network
    Ontario Institute for Cancer Research)

  • Amy Zhang

    (Ontario Institute for Cancer Research)

  • Lucy Ma

    (University Health Network)

  • Elena Elimova

    (University Health Network)

  • Raymond Jang

    (University Health Network)

  • Malcolm Moore

    (University Health Network)

  • James Biagi

    (Kingston Health Sciences Centre)

  • Mustapha Tehfe

    (Centre Hospitalier de l’Université de Montréal (CHUM))

  • Ravi Ramjeesingh

    (QEII Health Sciences Centre)

  • Erica S. Tsang

    (University Health Network)

  • Spring Holter

    (University Health Network)

  • Stephanie Ramotar

    (University Health Network)

  • Shawn Hutchinson

    (University Health Network)

  • Sheng-Ben Liang

    (University Health Network)

  • Ilinca M. Lungu

    (Ontario Institute for Cancer Research Toronto)

  • Shari Moura

    (University Health Network)

  • Yifan Wang

    (The Research Institute of the McGill University Health Centre
    The Rosalind & Morris Goodman Cancer Institute)

  • Sheron Perera

    (University Health Network)

  • Michelle Chan-Seng-Yue

    (Ontario Institute for Cancer Research)

  • Maryam Monajemzadeh

    (University Health Network)

  • Kyaw Aung

    (The University of Texas at Austin)

  • Rebecca Prince

    (University Health Network)

  • Joan Miguel Romero

    (The Research Institute of the McGill University Health Centre
    The Rosalind & Morris Goodman Cancer Institute)

  • Jesus Fuentes-Antras

    (University Health Network)

  • Galileo A. Gonzalez Conchas

    (University Health Network)

  • Sarah Picardo

    (University Health Network)

  • Ricardo Gonzalez

    (University Health Network)

  • Sangeet Ghai

    (University Health Network
    University of Toronto)

  • Korosh Khalili

    (University Health Network
    University of Toronto)

  • Tae Kyoung Kim

    (University Health Network
    University of Toronto)

  • Karen Ng

    (Ontario Institute for Cancer Research)

  • John Bartlett

    (University Health Network
    Western General Hospital)

  • Trevor J. Pugh

    (Ontario Institute for Cancer Research Toronto
    Princess Margaret Cancer Centre University Health Network)

  • Sangeetha N. Kalimuthu

    (University Health Network
    University Health Network)

  • Sandra E. Fischer

    (University Health Network
    University Health Network)

  • Julie M. Wilson

    (Ontario Institute for Cancer Research)

  • Anna Dodd

    (University Health Network)

  • George Zogopoulos

    (The Research Institute of the McGill University Health Centre
    The Rosalind & Morris Goodman Cancer Institute)

  • Barbara T. Grünwald

    (University Health Network
    University Hospital Essen
    West German Cancer Center)

  • Faiyaz Notta

    (University Health Network
    Ontario Institute for Cancer Research)

  • Steven Gallinger

    (University Health Network
    Ontario Institute for Cancer Research)

  • Grainne M. O’Kane

    (University Health Network
    University College Dublin)

Abstract

Integrated whole genome and transcriptome sequencing can unveil distinct molecular subgroups in pancreatic cancer (PDAC). The COMPASS trial (NCT02750657) enrolled 268 patients with advanced PDAC; patients were given either modified (m) FOLFIRINOX or Gemcitabine-nab-paclitaxel (GnP) as per physicians choice. Median follow-up is 52 months and median overall survival in those receiving mFOLFIRINOX is 10.6 months and 8.4 months for GnP. KRAS specific mutants and allelic states alone are not prognostic; however basal-like PDAC are more likely to harbour major imbalances in mutant KRAS (KRASmaj). In the presence of KRASmaj, pre-existing type II DM is more common. Distinct prognostic cohorts include homologous-recombination deficient PDAC, predictive of mFOLFIRINOX response. Basal-like PDAC and patients exhibiting evidence of systemic inflammation as annotated using the Gustave Roussy Immune Score are unique poor prognostic cohorts. The latter associates with low CD8 T cell infiltration while basal-like PDAC documents an inflamed tumour microenvironment.

Suggested Citation

  • Jennifer J. Knox & Gun Ho Jang & Robert C. Grant & Amy Zhang & Lucy Ma & Elena Elimova & Raymond Jang & Malcolm Moore & James Biagi & Mustapha Tehfe & Ravi Ramjeesingh & Erica S. Tsang & Spring Holter, 2025. "Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60808-z
    DOI: 10.1038/s41467-025-60808-z
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