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

• Published in: Nature Communications
• Main Authors: 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, Grainne M. O’Kane
• Format: Article
• Language: English
• Published: Nature Portfolio 2025-07-01
• Online Access: https://doi.org/10.1038/s41467-025-60808-z

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.