Abstract
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.
Highlights
Bladder cancer is the ninth most frequently diagnosed cancer worldwide, with incidence rates that are consistently lower in women than men
Caucasian patients with a diagnosis primary urothelial carcinoma of the bladder were enrolled in the study
Patients with concomitant of primary urothelial carcinoma of the bladder were enrolled in the study
Summary
Bladder cancer is the ninth most frequently diagnosed cancer worldwide, with incidence rates that are consistently lower in women than men. The highest rates are observed in men in Southern and Western Europe and North America [1] with 80,470 new cases in 2019; the estimated number of deaths in the USA was 17,670 [2]. In the European Union, the estimated number of new bladder cancer cases in 2018 was 19,710, with an estimation of 65% deaths [3]. Bladder cancer has the highest lifetime treatment costs per patient of all cancers, and costs have increased steadily since 1996. Despite significant improvements in preventing disease progression and improving survival, bladder cancer is characterized by a high rate of tumor recurrence and potential progression, regardless of treatment with surgery, chemotherapy, or immunotherapy [4].
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