The Clinical Significance Of P-STAT3、Survivin Expression In Bladder Urothelial Carcinoma

Objective:Signal transducers and activators of transcription 3(STAT3)have a dual role in signal transduction and transcriptional activation.Phosphorylation of STAT3(p-STAT3)has the ability to enter into the nucleus as a transcription factor and regulate downstream target genes in the nucleus--such as cell cycle regulatory factor:Cyclin D1,c-myc;apoptosis inhibitor:Bcl-X1,and survivin to promote cell cycle progression,apoptosis inhibition and angiogenesis.This study was to investigate the expression of p-STAT3 and Survivin in bladder urothelial cell carcinoma by immunohistochemistry and RT-PCR methods,and to explore p-STAT3 and Survivin expression in the development,clinical pathological characteristics,metastasis and prognosis of bladder urothelial cancer.Methods:We collected 77 cases of bladder urothelial carcinoma and 30 cases of normal bladder tissue samples far away adjacent>2cm as control from bladder cancer radical surgery from January 2012 to December 2015.Tissue microarray was maken.At the same time,within 77 cases of bladder cancer patients in our hospital,20 cases of fresh tumor tissues and normal adjacent tissues were collected.Detection of p-STAT3 and Survivin protein expression in paraffin embedded specimens of bladder cancer and normal tissues was performed by immunohistochemistry Envision two step method.The expression levels of mRNA STAT3 and mRNA Survivin in bladder carcinoma and normal tissues of fresh surgical specimens were detected by real-time PCR(RT-PCR)method.Immunohistochemical results were independently interpreted by two pathologists.Analysis of the relationship between p-STAT3,Survivin protein expression in bladder cancer and clinical pathological indicators was performed using SPSS 21 statistical software.Analysis of the relationship between p-STAT3,Survivin protein expression and the prognosis of patients with bladder cancer was performed by the method of Kaplan-Meier.Results:The positive rate of p-STAT3 protein in bladder cancer was 75.32%(58/77),and the positive rate was 6.67%(2/30)in the normal bladder tissues.There was a statistically significant difference between the two groups(P<0.05).The positive rate of p-STAT3 expression was significantly higher in the high grade urothelial carcinoma than in the low grade urothelial carcinoma(83.02%vs.58.33%,P<0.05).The 5 year survival rate of p-STAT3 protein positive patients was significantly lower than that of the negative patients(P<0.05).The p-STAT3 was closely related to the occurrence,histological grade and prognosis of bladder cancer,The positive rate of Survivin protein in bladder urothelial carcinoma was 71.42%(55/77),and no positivity was observed in 30 cases of normal bladder tissue.There was a statisticcally significant difference between the two groups(P<0.05).There is a significant difference in the positive expression of Survivin between age<63 years and over 63 years of bladder cancer(45.16%vs.89.13%,P<0.05).There was a significant difference for the positive expression of Survivin(45.83%vs.83.02%,P<0.05)in the low grade and high grade bladder cancer.There was a significant difference in the Survivin positive expression(positive rate of 53.57%,81.63%,P<0.05)in the non muscle invasive(Ta-T1)and the muscle layer infiltration(T2-T4).The 5 year survival rate of the negative expression of Survivin protein and positive expression were 81.81%and 50.90%,respectively.The difference was statistically significant(P<0.05).The results suggested that Survivin expression might be closely related to the occurrence,age,histological grade,invasion and prognosis of bladder cancer.The expression of p-STAT3 was positively correlated with the expression of Survivin(r=0.372).The relative quantitative results of STAT3 mRNA in bladder urothelial carcinoma was 2.39±0.85 and 1.00±0.24 in normal bladder tissue respectively.There was a statistically significant difference between the two groups(P<0.05).The relative quantitative result of Survivin mRNA in bladder urothelial carcinoma was 12.18± 4.76 and 1.00±0.71 in normal bladder tissue respectively.There was a statistically significant difference between the two groups(P<0.05).The relative quantitative results of RT-PCR were consistent with the results of immunohistochemistry protein expression.Conclusion:1.p-STAT3 was up-regulated expression in bladder urothelial carcinoma compared with peritumorial normal tissues.p-STAT3 was closely associated with bladder urothelial carcinoma occurrence,histological grade and prognosis.2.Survivin was up-regulated expression in bladder urothelial carcinoma compared with peritumorial normal tissues.Survivin was closely associated with bladder urothelial carcinoma occurrence,age,histological grade,muscle invasive and prognosis.3.p-STAT3 expression was positively correlated with Survivin expression in bladder urothelial carcinoma4.STAT3 mRNA and Survivin mRNA were up-regulated expression in bladder urothelial carcinoma compared with peritumorial normal tissues.