title: Urine gamma-synuclein as a biomarker for the diagnosis of bladder cancer.
abstract: Gamma-synuclein (SNCG) is secreted from tumor cells and elevated in the urine of bladder cancer (BCa) patients, however, the diagnostic and prognostic values of urine SNCG for BCa remain unknown. Here, we used enzyme immunoassay and western blotting to measure urine SNCG levels. Patients with BCa or other urological diseases and healthy controls were enrolled at four Chinese hospitals from April 2010 to November 2014. Diagnostic performance was evaluated by analyzing the area under receiver operating characteristic curves (AUROCs). The AUROC was 0.903 ± 0.019 (95% confidence interval [CI], 0.867 - 0.940) for the test and 0.929 ± 0.015 (95% CI, 0.901 - 0.958) for the validation cohort. The optimal cutoff value yielded sensitivities of 68.4%, 62.4% and specificities of 97.4%, 97.8% for the test and validation cohort, respectively. Urine SNCG levels were decreased after tumor resection, but were higher in BCa patients with recurrence than those without (P = 0.001). The urine SNCG levels in patients with urological benign diseases were significantly lower than BCa patients (all P < 0.05) but higher than healthy controls (all P < 0.05). Hematuria did not interfere with the SNCG detection by spiking urine specimens with whole blood. Compared with a nuclear-matrix-protein-22 assay in an additional cohort excluding hematuria, SNCG showed a similar sensitivity and higher specificity. In summary, our results demonstrated that urine SNCG can discriminate BCa from urinary diseases, and is a useful prognosticator of postsurgical recurrence.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.|Department of Biochemistry & Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Clinical Laboratory, Shanxi Provincial People's Hospital, Taiyuan, China.
authors.forename: Chonghua
authors.initials: C
authors.lastname: Hao
authors.affiliation: Department of Kidney Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Nianzeng
authors.initials: N
authors.lastname: Xing
authors.affiliation: Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shou
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.|Department of Biochemistry & Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.|Department of Biochemistry & Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine; D015153:Blotting, Western; D003558:Cystoscopy; D004797:Enzyme-Linked Immunosorbent Assay; D006417:Hematuria / Q000652:urine*; D006801:Humans; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000652:urine*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000652:urine*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000601:surgery / Q000652:urine*; D051845:gamma-Synuclein / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C104249:SNCG protein, human; D051845:gamma-Synuclein; C100379:nuclear matrix protein 22
keywords: bladder cancer; diagnosis; gamma-synuclein; prognosis; urine