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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • 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

摘要

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.