Integrated targeted metabolomic and lipidomic analysis: A novel approach to classifying early cystic precursors to invasive pancreatic cancer

Rogier Aäron Gaiser, Alberto Pessia, Zeeshan Ateeb, Haleh Davanian, Carlos Fernández Moro, Hassan Alkharaan, Katie Healy, Sam Ghazi, Urban Arnelo, Roberto Valente, Vidya Velagapudi, Margaret Sällberg Chen, Marco Del Chiaro

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from low-grade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. Accurate discrimination of IPMN-associated neoplastic grade is an unmet clinical need. Targeted (semi)quantitative analysis of 100 metabolites and >1000 lipid species were performed on peri-operative pancreatic cyst fluid and pre-operative plasma from IPMN and serous cystic neoplasm (SCN) patients in a pancreas resection cohort (n = 35). Profiles were correlated against histological diagnosis and clinical parameters after correction for confounding factors. Integrated data modeling was used for group classification and selection of the best explanatory molecules. Over 1000 different compounds were identified in plasma and cyst fluid. IPMN profiles showed significant lipid pathway alterations compared to SCN. Integrated data modeling discriminated between IPMN and SCN with 100% accuracy and distinguished IPMN LGD or IPMN HGD and invasive cancer with up to 90.06% accuracy. Free fatty acids, ceramides, and triacylglycerol classes in plasma correlated with circulating levels of CA19-9, albumin and bilirubin. Integrated metabolomic and lipidomic analysis of plasma or cyst fluid can improve discrimination of IPMN from SCN and within PMNs predict the grade of dysplasia.
Original languageEnglish
Article number10208
JournalScientific Reports
Volume9
Number of pages12
ISSN2045-2322
DOIs
Publication statusPublished - 15 Jul 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 3122 Cancers
  • Pancreatic cancer
  • Intraductal papillary mucinous neoplasms
  • Serous cystic neoplasm
  • Pancreatic cyst

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