Abstract B066: New Diagnostic Biomarkers for Malignant/Mucinous Pancreatic Cysts using Lipidomics

Lack of reliable early diagnosis tools for pancreatic ductal adenocarcinoma (PDAC) is a continuing challenge. Pancreatic mucinous cysts are known precursors for PDAC. However, most of these cysts do not progress to PDAC. Currently available diagnostic method to distinguish malignant pancreatic cyst is limited with low diagnostic accuracy. Our goal is to find a diagnostic method that is clinically feasible and accurate. Recent studies have shown that PDAC progression is mediated by altered metabolic pathways, and metabolites can serve as potential diagnostic markers. In this study, we collected 60 human pancreatic cyst fluid samples from surgical resection or endoscopic ultrasound-guided fine needle aspiration. The samples had known histologic diagnosis (24 benign and 28 malignant cysts; 10 non-mucinous and 47 mucinous cysts). We isolated both organic and inorganic compounds from the cyst samples to perform targeted and untargeted lipidomic profiling and data analysis. We annotated the untargeted analysis using different software, including Compound DiscovererTM 3.4 and LipidSearchTM. Based on the list of annotated compounds, we performed biomarker analysis (MetaboAnalyst 6.0) to find compounds with the highest area under the receiver operating characteristic curve (ROC AUC) scores. There were a few candidate metabolite compounds that had good potentials to serve as biomarkers for malignant/mucinous pancreatic cyst. For example, sphingomyelin SM(d16:1/25:0).1 (AUC score = 0.84) and 20:3-Glc-Campesterol (AUC score = 0.83) had greater than AUC score of 0.8 when classifying malignant cysts from benign. Potential biomarkers for mucinous cyst included sulfoglycosphingolipid ((3'-sulfo)Galbeta-Cer(d18:1/24:0(2OH))) (AUC score = 0.86) and phosphatidylcholine O-38:5.2 (AUC score = 0.84). The potential biomarkers will be validated with targeted standards using LC-MS/MS method. Taken together, lipids can serve as biomarkers for identifying malignant/mucinous pancreatic cyst which can, in turn, be used as an early detection method for PDAC. Citation Format: Hongsun C. Kim, Li Zhang, Costas A. Lyssiotis, JIaqi Shi. New Diagnostic Biomarkers for Malignant/Mucinous Pancreatic Cysts using Lipidomics [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B066.