Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial
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 (KRAS<sup>maj</sup>). In the presence of KRAS<sup>maj</sup>, 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.
Authors
- Sarah Picardo
- Malcolm J. Moore (ORCID: https://orcid.org/0009-0007-7493-3558)
- Joan Miguel Romero (ORCID: https://orcid.org/0000-0002-4123-0051)
- Erica S. Tsang (ORCID: https://orcid.org/0000-0003-2317-2721)
- Shawn Hutchinson (ORCID: https://orcid.org/0000-0002-2435-7114)
- Steven Gallinger (ORCID: https://orcid.org/0000-0002-6998-9414)
- Grainne M. O’Kane (ORCID: https://orcid.org/0000-0002-8690-403X)
- Raymond Jang (ORCID: https://orcid.org/0000-0003-1504-5175)
- Sangeetha Kalimuthu (ORCID: https://orcid.org/0000-0002-2115-3757)
- James Biagi (ORCID: https://orcid.org/0000-0001-9233-7396)
- Jesús Fuentes‐Antrás (ORCID: https://orcid.org/0000-0001-5805-2362)
- Michelle Chan‐Seng‐Yue (ORCID: https://orcid.org/0000-0003-3773-9354)
- Anna Dodd (ORCID: https://orcid.org/0000-0003-0649-0760)
- Sheng‐Ben Liang (ORCID: https://orcid.org/0000-0002-3251-8387)
- George Zogopoulos (ORCID: https://orcid.org/0000-0002-0482-7086)
- Amy Xian Zhang (ORCID: https://orcid.org/0000-0001-9462-9835)
- Sangeet Ghai (ORCID: https://orcid.org/0000-0001-9451-0594)
- Lucy Ma
- Karen Ng (ORCID: https://orcid.org/0009-0007-2217-3446)
- Barbara T. Grünwald (ORCID: https://orcid.org/0000-0002-7541-5206)
- Sheron Perera (ORCID: https://orcid.org/0000-0001-8048-0611)
- Ravi Ramjeesingh (ORCID: https://orcid.org/0000-0001-5584-3505)
- Maryam Monajemzadeh (ORCID: https://orcid.org/0000-0003-2642-9713)
- Faiyaz Notta (ORCID: https://orcid.org/0000-0002-5748-3985)
- Rebecca M. Prince (ORCID: https://orcid.org/0000-0002-7989-6537)
- Kyaw Lwin Aung (ORCID: https://orcid.org/0000-0001-9889-0379)
- Jennifer J. Knox (ORCID: https://orcid.org/0000-0003-3474-6647)
- Mustapha Tehfé (ORCID: https://orcid.org/0000-0002-1380-5110)
- Trevor J. Pugh (ORCID: https://orcid.org/0000-0002-8073-5888)
- Ilinca M. Lungu (ORCID: https://orcid.org/0000-0002-9996-5771)
- Julie M. Wilson (ORCID: https://orcid.org/0000-0003-2510-962X)
- Shari Moura (ORCID: https://orcid.org/0000-0001-5928-3568)
- Sandra Elisabeth Fischer (ORCID: https://orcid.org/0000-0001-8859-4525)
- Korosh Khalili (ORCID: https://orcid.org/0000-0002-3496-8744)
- Robert C. Grant (ORCID: https://orcid.org/0000-0002-9821-0377)
- John M.S. Bartlett (ORCID: https://orcid.org/0000-0002-0347-3888)
- Gun Ho Jang (ORCID: https://orcid.org/0000-0001-8169-7011)
- Stephanie Ramotar (ORCID: https://orcid.org/0000-0001-7619-2684)
- Galileo Arturo Gonzalez Conchas
- Yifan Wang (ORCID: https://orcid.org/0000-0003-2821-1953)
- Tae Kyoung Kim (ORCID: https://orcid.org/0000-0001-5193-1428)
- Ricardo González (ORCID: https://orcid.org/0000-0003-3853-2582)
- Spring Holter
- Elena Elimova
Institutions
- Ontario Institute for Cancer Research (CA)
- Livestrong Foundation (US)
- Capital District Health Authority (CA)
- University Health Network (CA)
- Western General Hospital (GB)
- Queen Elizabeth II Health Sciences Centre (CA)
- McGill University Health Centre (CA)
- Edinburgh Cancer Research (GB)
- Princess Margaret Cancer Centre (CA)
- Institute for Research in Immunology and Cancer (CA)
- St. Vincent's University Hospital (IE)
- Essen University Hospital (DE)
- Centre Hospitalier de l’Université de Montréal (CA)
- Kingston Health Sciences Centre (CA)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1038/s41467-025-60808-z
- Citations
- 15
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 15.68
Funders
- Princess Margaret Cancer Foundation
- Government of Ontario
- Hebrew University of Jerusalem
- Canadian Cancer Society Research Institute