RNA-seq Analysis of KRAS Mutant HPNE Pancreatic Ductal Epithelial Cells

Here, we investigate the early transcriptional impact of distinct KRAS mutants in a non-cancerous pancreatic epithelial context. Using RNA-seq, we profiled HPNE cells engineered with inducible KRAS variants (G12D, G12V, G12R, Q61H, Q61K, Q61R) compared to wild-type KRAS (WT) following 24-hour induction.

This comparative analysis reveals that KRAS mutations differentially regulate immune and extracellular matrix remodeling pathways, with G12D and Q61R/H mutants driving pro-inflammatory signaling, while G12R and Q61k exhibits distinct transcriptional suppression. These findings highlight the mutation-specific transcriptional landscapes of KRAS in pancreatic epithelial cells and provide insight into the early events shaping the pancreatic tumor microenvironment.