Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Titel eines Journals oder einer Zeitschrift: | Gastroenterology | ||||
Verlag: | W B SAUNDERS CO-ELSEVIER INC | ||||
Ort der Veröffentlichung: | PHILADELPHIA | ||||
Band: | 161 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 3 | ||||
Seitenbereich: | 910-923.e19 | ||||
Datum: | 2021 | ||||
Institutionen: | Medizin > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin | ||||
Identifikationsnummer: |
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Stichwörter / 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 | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 56439 |
Zusammenfassung
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 ...
Zusammenfassung
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.
Metadaten zuletzt geändert: 29 Feb 2024 12:28