Application Value Of Urine Modified Nucleosides’ Detection In Prognosis Of Bladder Urothelial Cell Carcinoma

Background and objectiveBladder cancer is the most common urothelial tumors. It is in the increasing trend in recent years in the world. However, it caused heavy economic burden to patients, such as in the diagnose、 remedy and recurrence surveillance and curing the complication.The researches indicated that the recurrence rate of bladder cancer was up to50%-90%in5years.About35%non-muscle invasive bladder cancer patients’ grade and periodization will be raised when it recurrenced,and about10%-20%patients could develop to muscle invasive bladder cancer.These patients must be operated by radical cystectomy and urinary diversion surgery, and it would appear some complications such as uroclepsia、dysury、sexual dysfunction and so on. The patients’social activities and the quality of life will be seriousiy impacted impacted. Therefore, early diagnose and forecast the recurrence of bladder cancer effectively is a urgent problem in clinical.At present, the major tumor markers which predict recurrence of bladder cancer risk are the gene products, and the main is protein,and the rest are some enzymes.These tumor markers are mostly macromolecules and vulnerable to be destructed by enzymes, they can not be kept well and need more blood samples, and sampling is not convenient, and especially for the bladder cancer of prognosis of low recurrence classification,the detection rate is low and the cost is very high.The modified nucleosides are in the RNA, which is formed by various specific modification enzymes after transfer acting on poly-1-nucleosides. The modified nucleosides also have many superiority, such as small molecular weight、stable structure and it is hard to react and modifying shape,and samples are easy to save and can be collected in urine、easy to collect and no damage、the tumors pedigree which is detected is popular and so on. Modified nucleosides as a tumor marker which have great potential are discovered playing a positive role in many aspectes such as the diagnose of cancer、monitor of illness and acquaintance the curative effect.Though detected the change of levels of m1A、ac4c、A、06-MeG、MTA、1-MEI、1-MEG in bladder cancer patients and the normal of our early study, we found that four modified nucleosides’levels were higher than the normal’s, They were m1A、ac4、06-MEG、1-MEI. The detection of M1A uniting1-MeI had high sensitivity (92.45%) and specificity (87.50%), and they could be the first select umor markers for BUCC.Therefor, urine modified nucleosides as a tumor markers have a broad prospects in clinical practice.This research is designed to detected the change of different levels of two modified nucleosides(M1A、1-MEI) in bladder cancer patients who were after the surgery and the normal at the different clinical stages and the patients who were after the surgery were in different pathology grades and clinical stages, and in order to find out the value of the detection in bladder cancer monitoring and provide a new method of detection in prognosis of patients with bladder cancer.MethodsWe enrolled85patients with bladder urothelial cell carcinoma (BUCC) confirmed by pathological examination.The85patients were fulfilled one year follow-up visit after TUR-BT and reviewed every three months.The muscle invasive cancer patients who were poor of the body condition or insisted on choosing this operation were operated by TUR-BT.The85patients did not relapse in the third month after operation.In the sixth monthafter operation20examples relapsed.18examples and19examples relapsed respective in the ninth month and the twelfth month after operation. Patients with recurrent add up to57examples as a recurrence group. The remaining28cases did not relapse in one year after operation as a not recurrence group. In85examples clinical stage55examples are Tis-T1, while30examples are T2-T4. In85examples pathology grade27examples are G1,40examples G2and18examples G3. In Tis-T1recurrence group are35examples, while a not recurrence group20examples. In T2-T4recurrence group are22examples,while a not recurrence group8examples.The50examples in the ordinary person are a control group. High-performance liquid chromatography/electrospray ionization-quadrupole-time-of-flight mass spectromerry was used to measure the levels of change of two urine modified nucleosides (M1A、1-MeI) which the patients with bladder cancer had different pathology grades、clinical stages,before or after operation and recurrence or not recurrence.Results1. The levels of change of two urine modified nucleosides in different time before and after operation have statistical significance (m1A:F=13.707,P<0.05,1-MeI:F=46.760,P<0.05). The levels of the third month after operation in not recurrence group(m1A:3.24±0.40,1-MeI:5.73±0.67)significantly lower than before operation (m1A:4.34±0.98,1-MeI:14.22±4.05P<0.005).The levels of the third month after operation in recurrence group (m1A:3.31±0.33,1-MeI:5.67±0.55) also significantly lower than before operation(m1A:4.32±1.19,1-MeI:14.31±4.12P<0.005).2. The levels of the third month、the sixth month、the ninth month、the twelfth month after operation in not recurrence group(M1A:3.24±0.40、3.26±0.24、3.38±0.31、3.27±0.27;1-MEI:5.73±0.67、5.84±1.10、5.66±0.73、5.78±0.66) significantly lower than before operation. But there were no changes at different points in time after operation (P>0.005). The trend of total levels change after operation peformed fall and maintained in a low condition. 3. The levels of the sixth month、the ninth month、the twelfth monthafter operation inrecurrence group (MIA:4.04±0.48、4.11±0.47、4.09±0.53,1-MEI:11.46±1.34、12.14±1.22、12.33±1.27) had no significantly change (P>0.005).The levels compared with the third monthafter operation inrecurrence groupsignificantly higher than it.The trend of total levels change after operation peformed first decreased and then increased and maintained at a high level of status and close to the preoperative level.4. Preoperative time points, without recurrence and relapse group was higher than the control (mlA:2.91±0.84,1-MeI:5.56±1.25P<0.01).The levels of the sixth month、the ninth month、the twelfth monthafter operation at all time points are recurrent group was the highest.5. The levels of change of G1、G2、G3grade (MIA:5.10±1.93、4.72±1.71、5.26±2.13;1-MEI:16.52±8.11、14.22、7.65、13.43、6.57) had no statistical significance (P>0.01). The levels of change ofTis-T1and T2-T4clinical stage (MIA:4.77±1.43、4.82±1.38;1-MEI:15.13±5.87、16.32±6.41)also had no statistical significance(P>0.01).The levels in recurrence group in Tis-T1(mlA:5.92±1.28,1-MeI:20.01±8.53) were higher than the levels in not recurrence group (mlA:4.02±1.22,1-MeI:11.21±6.45P<0.05), which is the same in T2-T4.Conclusion1. The levels of change of M1A and1-MEI, that two kinds of urine modified nucleoside levels in the assessment of treatment efficacy as well as monitoring the condition changes.2. Two kinds of urinary modified nucleoside levels’detection can judge the prognosis of recurrence risk for the bladder cancer patients.