Explore Of Molecular Markers In Bladder Cancer And The Clinical Significance Of Urine SNCG Test

Background and purpose:Bladder cancer is a threat to human health, is one of the most common malignancy of the urinary system, the incidence and mortality is rising. Due to the increasing and high recurrence rate of bladder cancer, making it one of the highest burden of cancer in urologists and patients. Currently cystoscopy in bladder cancer is still the gold standard for diagnosis and follow-up, but cystoscopy is invasive examination, caused great pain to the patient; while cytology has low sensitivity. There are no ideal molecular markers for clinical application. Therefore, the search for new tumor markers to improve the accuracy of diagnosis of bladder cancer is an urgent need to address the problem.Methods:First, we retrospectively studied the clinical data of patients with bladder cancer in Peking Union Medical College Hospital.A total of 140 cases of bladder cancer patients was collected, the clinical pathology and complete follow-up data for more than 5 years, and the paraffin sections available from these patients, a retrospective the SNCG, ARD1 and PRL-3 expression in bladder carcinoma and its relationship with clinicopathological features and bladder cancer prognosis; secondly, we chose SNCG for the study for the highest expression in bladder carcinoma, further exploration studied the serum and urine protein SNCG in 76 patients with bladder cancer, and found that bladder cancer cells can directly secreted SNCG protein and urine SNCG is higher than serum levels; and finally, to study the clinical value of urine SNCG testing, we performed a large-scale, multi-center cohort study to verify the urine SNCG value as a bladder cancer diagnosis and postoperative monitoring tools, and a comparative study with the NMP22.ResultsSNCG protein expression rate in 140 cases of bladder cancer was 90.7%(127/140); ARD1 protein expression was 80.7%(113/140); PRL-3 protein expression was 17.1% (24/140). Bladder cancer SNCG protein expression is more complex, there is the nucleus expression, but also filled with cytoplasm and cell membrane expression, the overall positive rate is higher, and bladder cancer cells to self-prompted SNCG protein secretion. Application of this paper obtained the first evidence monoclonal anti SNCG SNCG protein can be secreted from the MCF7-SNCG cells into the extracellular culture supernatant, the proof SNCG is a secreted protein, and tumor cell-specific expression of the protein, the bladder cancer SNCG cells secrete into the blood can either secreted directly into the urine surrounding the tumor. Serum SNCG bladder cancer patients was significantly higher than normal, but the same concentration in the urine of same patients,the SNCG was significantly higher than serum levels. And the detection level SNCG double-antibody sandwich ELISA which we have established is specificity, stability and reliability. Urine SNCG concentration was significantly higher in BCa patients than in age- and sex-matched healthy controls. The area under the ROC curve for SNCG was 0.903±0.019 (95% confidence interval (CI),0.867 to 0.940) in test cohort, 0.929±0.015 (95% CI,0.901 to 0.958) in validation cohort. An optimal cutoff value of 1.874 ng/mL resulted in sensitivity and specificity of 68.4%/97.4% in test and 62.4%/97.8% in validation cohort. Furthermore, we found urine SNCG decreased after resection of tumor from BCa patients, but was higher in recurrent patients (17.18±44.19 ng/ml) than in those without evidence of disease (2.81±11.95 ng/ml, P=.001). SNCG had lower sensitivity (46.2% v 56.4%, P=.344) and higher specificity (74.5% v 51.0%, P=.008) than NMP22 in a small cohort. Moreover, we demonstrated hematuria did not affect SNCG detection.ConclusionAs a secreted protein, SNCG not only have a high expression in bladder cancer tissue, but also have a higher expression in the urine of bladder cancer patients.Urine SNCG has the potential to discriminate BCa patients from healthy people and patients with benign urological diseases,And hematuria did not influence urine SNCG detection. SNCG has the value of early diagnosis of bladder cancer,also has monitoring role in bladder cancer recurrence. SNCG expression related with cancer cell proliferation, metastasis, and drug resistance. SNCG levels can predict the prognosis of cancer patients; suppression SNCG activity can increase the sensitivity of chemotherapy drugs, therefore SNCG is expected to become molecular marker and potential therapeutic target of bladder cancer.