FNA-based lipidomics reveals coordinated lipid metabolic remodeling in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is routinely used for preoperative tissue confirmation; however, its potential for comprehensive lipidomic profiling in a preoperative diagnostic setting remains insufficiently explored. Given the critical role of lipid metabolic reprogramming in PDAC progression, we investigated whether lipidomic alterations could be reliably captured in EUS-FNA-derived specimens.

Paired tumor and adjacent non-tumor tissues obtained via EUS-FNA from 13 PDAC patients were subjected to widely targeted (pseudo-targeted) liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomic analysis. Differential lipid species were identified through multivariate and univariate analyses. A composite lipid score was constructed based on principal component loadings. Serum samples from an independent cohort of 30 PDAC patients were included for exploratory projection analysis.

A total of 1822 lipid species across 47 lipid classes were detected in EUS-FNA-derived specimens. Tumor tissues displayed coordinated lipid alterations, including accumulation of storage lipids and structural remodeling of fatty acyl chains characterized by elongation and increased unsaturation. These alterations were readily detectable in EUS-FNA-derived specimens. These patterns showed a tendency to distinguish tumor from adjacent non-tumor samples within the FNA cohort. Exploratory projection suggested directionally consistent lipid changes in serum samples.

Lipid metabolic remodeling in PDAC can be reliably detected in preoperative EUS-FNA-derived specimens. These findings support the feasibility of lipidomic profiling in minimally invasive diagnostic samples and highlight the translational potential of EUS-FNA-based metabolic assessment.