Expression Of Survivin And Its Splice Variants Survivin-2B And Survivin-△Ex3 In Bladder Cancer And Clinical Significance

Objective The morbility of bladder cancer is in the eight position all over the body malignant tumors in the world,and in the first position of genitourinary in China.Bladder cancer has a high risk of recurrence rate,and 10%-20%of superficial bladder cancer will develop into infiltrating type.Up to date,there is still lack of an ideal detection method for anticipating progress and recurrence rate of bladder cancer.Survivin gene is a member of inhibitor of apoptosis proteins(IAPs).Multiplicity researches certified the significance of survivin in tumorigenesis and development of bladder cancer,but seldom of its splice variants.To continue former researches,we studied the expression of survivin mRNA and its two splice variants survivin-2B mRNA and survivin-△Ex3 mRNA in transitional cell carcinoma of bladder(TCC),and on the basis of follow-ups,comprehended the relation of their expression levels with the tumorigenesis,development and prognosis of TCC.Methods The fresh carcinoma tissues of 60 patients with TCC and 12 innocence bladder affection tissues were detected the relative amount of survivin mRNA,survivin-2B mRNA and survivin-△Ex3 mRNA by real-time quantitative reverse transcription polymerase chain reaction(RT-PCR).The amplification-production by PCR was depurated and sequenced.The patient group could be divided into three subgroups according to the pathologic grades:Ⅰ(19samples),Ⅱ(29 samples)andⅢ(12 samples),and two subgroups according to the depth of tumor invasive:A(no muscle invasive)43 samples,B(muscle invasive)17 samples.The time of follow-up was 4-24 months.Results Survivin,survivin-2B,survivin-△Ex3 mRNA were detected in all the 60 TCC tissues,their relative expression levels were:0.333±0.163,0.056±0.017,0.124±0.096.In the control group,three and four samples expressed survivin and survivin-△Ex3mRNA respectively,and all samples expressed survivin-2B mRNA.The survivin,survivin-2B, survivin-△Ex3mRNA expression levels were higher in the patient group than in the control group(P＜0.05).Different expression levels of survivin mRNA could be observed among different pathologic grades,gradeⅠ:0.170±0.046,gradeⅡ:0.353±0.069,and gradeⅢ:0.543±0.179.The differences among pathological grades were statistically significant (P＜0.05).The expression of survivin mRNA also differed between different tumor invasive groups,A:0.270±0.108,B:0.494±0.170(P＜0.05).The expression of survivin mRNA was well relation with the pathologic grades and depth of tumor invasive(0＜r'_s＜1,P＜0.05). Survivin-2BmRNA was:gradeⅠ:0.074±0.015,gradeⅡ:0.051±0.011,and gradeⅢ: 0.040±0.006;A:0.062±0.017,B:0.043±0.009.The differences among the different pathological grades and tumor invasive groups were statistically significant(P＜0.05).The expression of survivin-2BmRNA was negativity relation with the pathologic grades and depth of tumor invasive(-1＜r'_s＜0,P＜0.05).Survivin-△Ex3mRNA was:gradeⅠ: 0.082±0.014,gradeⅡ:0.086±0.011,and gradeⅢ:0.285±0.115;A:0.085±0.013,B: 0.225±0.135.The differences between pathological gradeⅡ,Ⅲand tumor invasive groups were statistically significant(P＜0.05).The ratios of survivin-2B/ survivin was:gradeⅠ: 0.465±0.156,gradeⅡ:0.149±0.037,and gradeⅢ:0.083±0.033;A:0.290±0.190,B: 0.099±0.042.The differences among pathological grades and tumor invasive groups were statistically significant(P＜0.05),and negativity relationship tendency(-1＜r_s＜0,P＜0.05). The differences between pathological grades and tumor invasive of the ratios of survivin-△Ex3/survivin were no statistically significant(P＞0.05).In 47 follow-ups,3 patients recurred TCC after 5,11,9 months,respectively.Unexpectedly,the ratios of survivin-2B/survivin of former tissues of these patients(gradeⅡ:0.052,0.075,gradeⅢ: 0.051)were lower than the same pathological grade(gradeⅡ:0.149±0.037,gradeⅢ: 0.083±0.033)significantly.Conclusion 1.There was certainty transcription expression of survivin and its splice variants survivin-△Ex3 and survivin-2B in TCC tissues.2.The higher the expression levels of survivin was,the more differentiate and malignant degree the TCC was.For infiltrative TCC,survivin was over- expressed,which suggests that TCC was more likely to infiltrate and had unfavourable prognosis.3.In the tumorigenesis and proceeding of TCC,survivin-△Ex3 and survivin-2B maybe educe different roles.The transcription expression of survivin-△Ex3 was increasing in high grade and poorly differentiated TCC remarkably,and well relationship with grades of pathology and infiltration,while survivin-2B was negativity,which suggested that survivin-△Ex3 and survivin-2B could predict prognosis of TCC.4.The ratios of survivin-2B/survivin in 3 recrudescence patients were obviously lower than the same pathology grades,which indicated the degression ratios of survivin-2B/survivin was related with high risk recurrence rate of TCC.The detection of survivin and survivin-2B mRNA in TCC tissues by real-time quantitative RT-PCR could provid a worth index for predicting recurrence rate,and a objective reference for projecting follow-up time and chemotherapy in clinic.5.The expression levels of survivin-2B might be relation with proliferation and differentiation of bladder epithelial cells.And survivin-2B might have different roles in regulating growth, differentiation and malignant transformation of bladder epithelial cells.6.The expression levels of survivin and its two splice variants survivin-2B and survivin-△Ex3 in TCC could have potential values to appraisal tumor progression and recurrence rate of TCC.