Ecker, Josef and Benedetti, Elisa and Kindt, Alida S. D. and Hoering, Marcus and Perl, Markus and Machmueller, Andrea Christel and Sichler, Anna and Plagge, Johannes and Wang, Yuting and Zeissig, Sebastian and Shevchenko, Andrej and Burkhardt, Ralph and Krumsiek, Jan and Liebisch, Gerhard and Janssen, Klaus-Peter (2021) The Colorectal Cancer Lipidome: Identification of a Robust Tumor-Specific Lipid Species Signature. GASTROENTEROLOGY, 161 (3). 910-+. ISSN 0016-5085, 1528-0012
Full text not available from this repository. (Request a copy)Abstract
OBJECTIVE: Lipidomic changes were causally linked to meta-bolic 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 comprehen-sive 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 (Apc(1638N)). RESULTS: Significant differences were found between tumor and normal tissue for glycero-, glycer-ophospho-, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TANDEM MASS-SPECTROMETRY; HIGH-THROUGHPUT QUANTIFICATION; POLYUNSATURATED FATTY-ACIDS; HILIC-HPLC/ESI-MS; METABOLISM; RISK; PHOSPHATIDYLCHOLINE; DIFFERENTIATION; SPHINGOMYELIN; EXTRACTION; Biomarker; Mass Spectrometry; Signature; Sphingo-myelin; Triacylglycerol |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2022 07:26 |
| Last Modified: | 20 Sep 2022 07:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47614 |
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