Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder.
Eur Urol Focus
; 4(6): 907-915, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-28753886
ABSTRACT
BACKGROUND:
The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified.OBJECTIVE:
To identify lipidomic signatures associated with survival and different clinical stages of UCB. DESIGN, SETTING, ANDPARTICIPANTS:
Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75). RESULTS ANDLIMITATIONS:
UCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study.CONCLUSIONS:
To date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression. PATIENTSUMMARY:
Lipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfolípidos
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Triglicéridos
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Neoplasias de la Vejiga Urinaria
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Carcinoma de Células Transicionales
/
Ácidos Grasos
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
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Male
Idioma:
En
Revista:
Eur Urol Focus
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos