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Open AccessArticle

Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage

Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Hospital, 20132 Milano, Italy
Università Vita-Salute San Raffaele, 20132 Milano, Italy
Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Sezione di Tossicologia Forense, Università degli Studi di Milano, 20133 Milano, Italy
Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università degli Studi di Milano, 20157 Milano, Italy
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 870;
Received: 18 February 2020 / Revised: 12 March 2020 / Accepted: 1 April 2020 / Published: 3 April 2020
(This article belongs to the Special Issue Non-Invasive Early Detection of Cancers)
Due to the involvement of the endocannabinoid system (ECS) in cancer onset and progression and the less studied connection between ECS and bladder cancer, here an evaluation of the ECS modifications associated with bladder cancer is reported. Urine samples were collected from healthy volunteers and patients with bladder cancer at different grades. Endocannabinoids (ECs) and N-acylethanolamides (NAEs) were quantified by HPLC-MS/MS and results normalized for creatinine content. An increase in the urine concentrations of four ECs and NAEs analyzed was observed with a statistically significant increase in the arachidonoylethanolamide (AEA) and stearoylethanoamide (SEA) associated with bladder cancer. Receiver operating characteristic curves built with AEA and SEA data allowed the selection of 160 pg/mL for SEA (area under the curve (AUC) = 0.91, Selectivity (SE) 94%, Specificity (SP) 45%) and 8 pg/mL for AEA (AUC = 0.85, SE 94%, SP 61%) as the best cut-off values. Moreover, data from bladder cancer samples at different grades were derived from The Cancer Genome Atlas, and the expressions of thirteen different components of the “endocannabinoidome” were analyzed. Statistical analysis highlights significant variations in the expression of three enzymes involved in EC and NAE turnover in bladder cancer.
Keywords: bladder cancer; endocannabinoid system; endocannabinoid quantification; biomarkers bladder cancer; endocannabinoid system; endocannabinoid quantification; biomarkers
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MDPI and ACS Style

Vago, R.; Ravelli, A.; Bettiga, A.; Casati, S.; Lavorgna, G.; Benigni, F.; Salonia, A.; Montorsi, F.; Orioli, M.; Ciuffreda, P.; Ottria, R. Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage. Cancers 2020, 12, 870.

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