Research Papers:
Urine gamma-synuclein as a biomarker for the diagnosis of bladder cancer
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Abstract
Caiyun Liu1,2,*, Bingbing Shi3,*, Chonghua Hao4,*, Qinghai Wang5,*, Qiang Lv6,*, Nianzeng Xing7,*, Jianzhong Shou8,*, Like Qu1,2, Yanning Gao9, Chao Qin6, Jiyu Zhao7, Chengchao Shou1,2
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China
2Department of Biochemistry & Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China
3Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
4Department of Clinical Laboratory, Shanxi Provincial People’s Hospital, Taiyuan, China
5Department of Kidney Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, China
6Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
7Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
8Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
9Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China
*These authors have contributed equally to this work
Correspondence to:
Chengchao Shou, email: [email protected]
Keywords: urine, gamma-synuclein, bladder cancer, diagnosis, prognosis
Received: November 22, 2015 Accepted: March 29, 2016 Published: May 19, 2016
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.
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