Vago Riccardo, Ravelli Alessandro, Bettiga Arianna, Casati Silvana, Lavorgna Giovanni, Benigni Fabio, Salonia Andrea, Montorsi Francesco, Orioli Marica, Ciuffreda Pierangela, Ottria Roberta
Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Hospital, 20132 Milano, Italy.
Università Vita-Salute San Raffaele, 20132 Milano, Italy.
Cancers (Basel). 2020 Apr 3;12(4):870. doi: 10.3390/cancers12040870.
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.
由于内源性大麻素系统（ECS）参与癌症的发生和发展，且ECS与膀胱癌之间的联系研究较少，因此本文报道了对与膀胱癌相关的ECS变化的评估。从健康志愿者和不同分级的膀胱癌患者中收集尿液样本。通过HPLC-MS/MS对内源性大麻素（ECs）和N-酰基乙醇胺（NAEs）进行定量，并将结果根据肌酐含量进行标准化。观察到所分析的四种ECs和NAEs的尿液浓度增加，其中与膀胱癌相关的花生四烯酸乙醇胺（AEA）和硬脂酸乙醇酰胺（SEA）有统计学显著增加。用AEA和SEA数据构建的受试者工作特征曲线显示，SEA的最佳截断值为160 pg/mL（曲线下面积（AUC）= 0.91，选择性（SE）94%，特异性（SP）45%），AEA的最佳截断值为8 pg/mL（AUC = 0.85，SE 94%，SP 61%）。此外，不同分级膀胱癌样本的数据来自癌症基因组图谱，并分析了“内源性大麻素组”的13种不同成分的表达。统计分析突出了膀胱癌中参与EC和NAE代谢的三种酶的表达存在显著差异。
