Exploration of Lipid Mediators for Therapeutic Monitoring of Pancreatic Cancer Patients.

Background/aim: Multimodal treatment is now the primary strategy for managing pancreatic cancer. Blood-based protein markers are sometimes useless for evaluating the real-time disease condition to determine treatment strategies. This study focused on detecting novel exosomal lipid biomarkers, as exosomes contain several biological mediators.

Materials and methods: Lipidomic analysis was conducted by liquid chromatography-mass spectrometry (LC-MS) using serum exosome-derived lipid samples from four pancreatic ductal adenocarcinoma (PDAC) patients and four healthy controls. Some candidates were ascertained using multiple time-point blood samples from four additional PDAC patients. Furthermore, we validated them using an additional twelve multimodal-treated PDAC patient cohort.

Results: Nontarget LC-MS analysis revealed that lysophosphatidylcholine (LPC) expression levels were significantly decreased in PDAC patients compared to healthy controls. Multiple time-point blood samples demonstrated that LPC (16:0) and LPC (18:1) consistently showed lower levels in relapsed cases than in non-relapsed cases over time. In the validation cohort, a low LPC level before initial treatment was associated with histological lymphatic invasion (p=0.04) and was linked to progressive-free survival (PFS) (p=0.04).

Conclusion: PDAC patients with initially low LPC levels in the blood exosomes demonstrated an unfavorable PFS. Exosomal lipid markers may serve as potential indicators for disease monitoring in pancreatic cancer patients undergoing multimodal treatment.