The Colorectal Cancer Lipidome: Identification of a Robust Tumor-Specific Lipid Species Signature

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Josef Ecker - (Author)
  • Elisa Benedetti - (Author)
  • Alida S. D. Kindt - (Author)
  • Marcus Hoering - (Author)
  • Markus Perl - (Author)
  • Andrea Christel Machmueller - (Author)
  • Anna Sichler - (Author)
  • Johannes Plagge - (Author)
  • Yuting Wang - (Author)
  • Sebastian Zeissig - , Department of Internal Medicine I, Center for Regenerative Therapies Dresden (Author)
  • Andrej Shevchenko - (Author)
  • Ralph Burkhardt - (Author)
  • Jan Krumsiek - (Author)
  • Gerhard Liebisch - (Author)
  • Klaus-Peter Janssen - (Author)

Abstract

Objective: Lipidomic changes were causally linked to metabolic diseases, but the scenario for colorectal cancer (CRC) is less clear. We investigated the CRC lipidome for putative tumor-specific alterations through analysis of 3 independent retrospective patient cohorts from 2 clinical centers, to derive a clinically useful signature. Design: Quantitative comprehensive lipidomic analysis was performed using direct infusion electrospray ionization coupled with tandem mass spectrometry (ESI-MS/MS) and high-resolution mass spectrometry (HR-MS) on matched nondiseased mucosa and tumor tissue in a discovery cohort (n = 106). Results were validated in 2 independent cohorts (n = 28, and n = 20), associated with genomic and clinical data, and lipidomic data from a genetic mouse tumor model (Apc1638N). Results: Significant differences were found between tumor and normal tissue for glycero-, glycerophospho-, and sphingolipids in the discovery cohort. Comparison to the validation collectives unveiled that glycerophospholipids showed high interpatient variation and were strongly affected by preanalytical conditions, whereas glycero- and sphingolipids appeared more robust. Signatures of sphingomyelin and triacylglycerol (TG) species significantly differentiated cancerous from nondiseased tissue in both validation studies. Moreover, lipogenic enzymes were significantly up-regulated in CRC, and FASN gene expression was prognostically detrimental. The TG profile was significantly associated with postoperative disease-free survival and lymphovascular invasion, and was essentially conserved in murine digestive cancer, but not associated with microsatellite status, KRAS or BRAF mutations, or T-cell infiltration. Conclusion: Analysis of the CRC lipidome revealed a robust TG-species signature with prognostic potential. A better understanding of the cancer-associated glycerolipid and sphingolipid metabolism may lead to novel therapeutic strategies.

Details

Original languageEnglish
Pages (from-to)910-923.e19
JournalGastroenterology
Volume161
Issue number3
Publication statusPublished - Sept 2021
Peer-reviewedYes

External IDs

WOS 000687968400026
Scopus 85108223296

Keywords

Research priority areas of TU Dresden

Sustainable Development Goals

ASJC Scopus subject areas

Library keywords