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

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, Stephanie Ramotar, Shawn Hutchinson, Sheng-Ben Liang, Ilinca M. Lungu, Shari Moura, Yifan Wang, Sheron Perera, Michelle Chan-Seng-Yue, Maryam Monajemzadeh, Kyaw Aung, Rebecca Prince, Joan Miguel Romero, Jesus Fuentes-Antras, Galileo A. Gonzalez Conchas, Sarah Picardo, Ricardo Gonzalez, Sangeet Ghai, Korosh Khalili, Tae Kyoung Kim, Karen Ng, John Bartlett, Trevor J. Pugh, Sangeetha N. Kalimuthu, Sandra E. Fischer, Julie M. Wilson, Anna Dodd, George Zogopoulos, Barbara T. Grünwald, Faiyaz Notta, Steven Gallinger and Grainne M. O’Kane ()
Additional contact information
Jennifer J. Knox: University Health Network
Gun Ho Jang: Ontario Institute for Cancer Research
Robert C. Grant: University Health Network
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
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
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
Korosh Khalili: University Health Network
Tae Kyoung Kim: University Health Network
Karen Ng: Ontario Institute for Cancer Research
John Bartlett: University Health Network
Trevor J. Pugh: Ontario Institute for Cancer Research Toronto
Sangeetha N. Kalimuthu: University Health Network
Sandra E. Fischer: 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
Barbara T. Grünwald: University Health Network
Faiyaz Notta: University Health Network
Steven Gallinger: University Health Network
Grainne M. O’Kane: University Health Network

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60808-z

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