Reduced lipid metabolite abundance in human pancreatic cancer and matched serum samples following neoadjuvant FOLFIRINOX treatment.

[INTRODUCTION] Exploiting the full potential of neoadjuvant treatment (NAT) in pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of biomarkers for treatment response. Dysregulated lipid metabolism has been suggested to promote PDAC growth and resistance to therapy.

[OBJECTIVES] To investigate lipid metabolic changes in PDAC following NAT.

[METHODS] Cross-sectional study of mass spectrometry-based global lipidomic profiling of tumour tissue (n = 35) and paired serum samples (n = 35) from treatment-naïve (TN; n = 18) and neoadjuvant FOLFIRINOX-treated (NAT; n = 17) PDAC patients was conducted. Pre- and post-treatment CA 19-9 levels were available from 15 NAT patients. Differentially abundant lipids (DALs) in NAT versus TN were assessed for correlation with various clinical parameters and the performance of all serum DALs to distinguish NAT from TN samples was explored using receiver operating characteristic analysis.

[RESULTS] A total of 40 tissue and 35 serum DALs were identified, which mainly belonged to glycerophospholipids and sphingolipids in tissue and glycerolipids, glycerophospholipids, and fatty acyls in serum. All 19 serum glycerolipids were less abundant in NAT and 18 of these were triacylglycerols. The abundance of 26 tissue and 11 serum DALs correlated moderately with % reduction in serum CA 19-9 following NAT. The top five of 23 serum DALs with moderate discriminatory potential (AUC = 0.66-0.87) ‒ PI(18:0_20:3), AcCa(13:0), PC(O-42:6), TG(49:6), TG(66:14), performed better together (AUC = 0.93 and 95% CI = 0.79‒1) and combined with CA 19-9 (AUC = 0.99 and 95% CI = 0.81‒1).

[CONCLUSIONS] Both tumour tissue and serum samples from PDAC patients showed lower abundance of lipid metabolites following neoadjuvant FOLFIRINOX treatment. Moreover, a biomarker panel of CA 19-9 together with five serum DALs could potentially be used to assess NAT response in PDAC but requires further validation.