The Colorectal Cancer Lipidome: Identification of a Robust Tumor-Specific Lipid Species Signature.
Gastroenterology
; 161(3): 910-923.e19, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34000281
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Colon_e_reto
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Biomarcadores Tumorais
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Metaboloma
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Lipidômica
/
Lipídeos
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
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Aged80
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Animals
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Gastroenterology
Ano de publicação:
2021
Tipo de documento:
Article