Plasma metabolome profiling identifies metabolic subtypes of pancreatic ductal adenocarcinoma

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Ujjwal Mukund Mahajan - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Ahmed Alnatsha - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Qi Li - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Bettina Oehrle - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Frank Ulrich Weiss - , Ernst-Moritz-Arndt-Universität Greifswald (Autor:in)
  • Matthias Sendler - , Ernst-Moritz-Arndt-Universität Greifswald (Autor:in)
  • Marius Distler - , Klinik und Poliklinik für Viszeral- Thorax- und Gefäßchirurgie, Nationales Centrum für Tumorerkrankungen Dresden, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Waldemar Uhl - , Ruhr-Universität Bochum (Autor:in)
  • Tim Fahlbusch - , Ruhr-Universität Bochum (Autor:in)
  • Elisabetta Goni - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Georg Beyer - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Ansgar Chromik - , Asklepios Klinik Hamburg Nord-Heidberg (Autor:in)
  • Markus Bahra - , Krankenhaus Waldfriede (Autor:in)
  • Fritz Klein - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Christian Pilarsky - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Robert Grützmann - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Markus M. Lerch - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Kirsten Lauber - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Nicole Christiansen - , trinamiX GmbH (Autor:in)
  • Beate Kamlage - , Metanomics Health GmbH (Autor:in)
  • Ivonne Regel - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Julia Mayerle - , Ludwig-Maximilians-Universität München (LMU), Ernst-Moritz-Arndt-Universität Greifswald (Autor:in)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abun-dance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

Details

OriginalspracheEnglisch
Aufsatznummer1821
FachzeitschriftCells
Jahrgang10
Ausgabenummer7
PublikationsstatusVeröffentlicht - Juli 2021
Peer-Review-StatusJa

Externe IDs

PubMed 34359990

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Complex lipids, Metabolic subtypes, Pancreatic ductal adenocarcinoma, Sphingolipids