Genomic Implications of Transcriptional Subtypes in Pancreatic Cancer

Authors:

Harshabad Singh, Kevin Kapner, Joanne Xiu, Matthew Oberley, Alex Farrell, Jimmy Guo, Rishi Surana, Kimberly Perez, James Cleary, Srivatsan Raghavan, Benjamin Weinberg, Michael Pishvaian, Rachna Shroff, Sanjay Goel, Stephanie Dougan, Jonathan Nowak, David Spetzler, George Sledge, Brian Wolpin, Andrew Aguirre

Background/Methods:

  • Transcriptional profiling of pancreatic cancers (PC) has defined classical and basal subtypes
  • Basal subtypes have worse prognosis
  • Post therapy Mesenchymal (MES) and neural–like progenitor (NRP) states have been defined
  • Initial clinical data suggests differential response of transcriptional subtypes with FOLFIRINOX vs. Gemcitabine-nab-Paclitaxel (Gem/nab-P) in PC.
  • Basal tumors may preferentially response to Gem/nab-P Methods:  Genomic cohort: 7,250 PCs profiled by Caris Life Sciences
  • Clinical cohort: 1,623 PCs with additional clinical data available. Survival data was obtained from insurance claims data. Kaplan-Meier estimates were used for survival analysis.
  • Transcriptional cell states were identified using RNA-seq Results: 3,063 tumors (42.2%) were strongly classical (SC), 2,015 tumors (27.8%) were strongly basal (SB) • MES and NRP marker genes were significantly coexpressed with each other, with basal genes, and anti-correlated with classical genes.
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