Deciphering Fatty Acid Biosynthesis-Driven Molecular Subtypes in Pancreatic Ductal Adenocarcinoma with Prognostic Insights

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge due to its high heterogeneity and aggressiveness. Recognizing the urgency to delineate molecular subtypes, our study focused on the emerging field of lipid metabolism remodeling in PDAC, particularly exploring the prognostic potential and molecular classification associated with fatty acid biosynthesis. Here we identified a 7-gene signature associated with fatty acid biosynthesis-related genes (FRGs), providing a robust tool for survival prediction. The high- FRGs score group displayed a poorer prognosis, lower immune infiltration abundance, and a higher tumor mutational burden. Notably, ACSL5, a key gene in 7-gene signature panel was upregulated in PDAC. The biological function of ACSL5 were validated with in vitro assay. Finally, we unveiled that ACSL5 played a crucial role in pancreatic cancer progression, promoting tumor initiation, metastasis, and immune evasion. Overall design: To investigate the function of ACSL5 in the progression of PDAC, we examined ACSL5 knockdown and WT cell lines. Then, we performed RNA sequencing to analyze gene expression profile of ACSL5 knockdown and WT cells.