Proteomic analysis for human urinary proteins associated with arsenic intoxication

Abstract

Arsenic is widely distributed in nature and is mainly transported in the environment by water. Consumption of artesian well water with high levels of arsenic has been associated with genitourinary cancer, especially bladder transitional cell carcinoma (TCC). To search for biomarkers that are specific for arsenic associated with the diagnosis of bladder TCC, proteins in the urine of non-cancer urological patients and patients with either bladder TCC or arsenic-associated bladder TCC were systematically examined by HPLC ESI-MS/MS. Urine specimens were collected by catheterization from patients and age- (within 5 years) and sex-matched non-cancer urological patients. A nano-HPLC-ESI-MS/MS was used to generate proteome patterns from urine specimens obtained from patients with arsenic-associated (n = 8) and non-arsenic-associated (n = 8) primary TCC and from sex- and age-matched non-cancer urological patients (n = 8). Three urinary proteins were found to have significantly altered levels in patients following chronic arsenic exposure. These proteins were a disintegrin and metalloprotease (ADAM) protein, a calpain9, and ring finger protein 20. The large-scale identification of urinary proteomes using HPLC ESI-MS/MS may serve as an ideal and efficient method to establish a panel of potential arsenic-associated TCC biomarkers and may help elucidate the mechanisms involved in bladder cancer induced by chronic arsenic exposure.