Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration

In this study, we analyzed RNA sequencing data from TCGA datasets, comparing tumor versus normal pancreatic tissues and stratifying samples based on KRAS mutation status. Our findings reveal significant dysregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in PC, particularly in the context of KRAS mutations. These findings were validated through RT-qPCR in an independent cohort of primary samples. Key genes, including CD36, FABP4, PLIN1, PLIN4, SCD5, and ACSLs, were consistently downregulated in tumor tissues, with further reductions observed in KRAS-mutated samples. Overall, this study highlights the critical role of PPAR pathway disruption in KRAS-mutated PC, which should be further addressed to improve current treatment strategies.