Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Mahajan UM, Alnatsha A, Li Q, Oehrle B, Weiss FU, Sendler M, Distler M, Uhl W, Fahlbusch T, Goni E, Beyer G, Chromik A, Bahra M, Klein F, Pilarsky C, Grützmann R, Lerch MM, Lauber K, Christiansen N, Kamlage B, Regel I, Mayerle J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cells MDPI

Book Volume: 10

Journal Issue: 7

DOI: 10.3390/cells10071821

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(R) Global Profiling and MxP(R) 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 abundance 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.

Authors with CRIS profile

Christian Pilarsky Professur für Chirurgische Forschung Robert Grützmann Lehrstuhl für Allgemein- und Viszeralchirurgie

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Technische Universität Dresden DE Germany (DE) Asklepios Klinik Altona DE Germany (DE) trinamiX GmbH DE Germany (DE) Krankenhaus Waldfriede DE Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald DE Germany (DE)

How to cite

APA:

Mahajan, U.M., Alnatsha, A., Li, Q., Oehrle, B., Weiss, F.-U., Sendler, M.,... Mayerle, J. (2021). Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma. Cells, 10(7). https://dx.doi.org/10.3390/cells10071821

MLA:

Mahajan, Ujjwal Mukund, et al. "Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma." Cells 10.7 (2021).

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