Study On Expression Of STK 15 Gene In Human Bladder Cancer And Relationship Between Its Single Nucleotide Polymorphisms And Risk Of Bladder Cancer

Bladder transitional cell carcinoma is the most common urological malignant disease in the world. 70% of patients with bladder cancer have only noninvasive disease or tumors with invasion no deeper than the lamina propria on initial presentation, and 95% of patients with bladder cancer having noninvasive disease are high risky.As other tumors, bladder cancer takes several steps from normal cells to abnormal cells.There are kinds of genomic changes including oncogene, anti-onco-gene,cell cycle gene and DNA repair gene.STK15 is a kind of gene with centrosome.Many researchs find that STK15 may take gene amplification and overexpression in mammal cells, which induce the abnormality with centrosomal number, function, polypolor spindle, chromosome segregation and aneuploid.Researchers find that STK15 with overexpression in many tumors including esophagus cancer, brest cancer, ovary cancer, colorectal cancer, laryngeal squamous cancer, pancreatic cancer,prostate cancer, lung cancer and liver cancer.There are few researchs about bladder cancer in the world,and none of research about bladder cancer in china.It suggests that STK15 is very important in the many rumors,and we should invest how STK15 making in the development of bladder cancer.In order to study the expression of STK15 in human bladder carcinoma cell lines and in bladder cancer tissue,to know whether STK15 protein expression have relationship with the biological behaviors of BTCC,and to detect the association between STK15 Phe31 Ile polymorphism and bladder cancer. This research including three parts:1 The expression of STK15 in mRNA and protein level of bladder carcinoma cell lines (EJ, 5637, T24) was examined by semi-quantitative RT-PCR andWestem-blotting.2 Semi-quantitative RT-PCR was used to detect the expression of STK15 mRNA in bladder fresh tissue. Immunohistochemistry was used to detect the expression of STK15 protein in bladder transitional cell carcinoma (BTCC) tissue and normal bladder epithelial tissue. Study the molecular mechanism of BTCC all the better from these expression.3 A case-control study was designed to detect the association between STK15 Phe31Ile polymorphism and bladder cancer.PartⅠStudy on Expression of STK15 in human bladder carcinoma cell linesObjective:To study the expression of STK15 in human bladder carcinoma cell lines.Methods:The expression of STK15 in mRNA and protein level of bladder carcinoma cell lines (EJ, 5637, T24) was examined by semi-quantitative RT-PCR and Western-blotting and the result was analysed with BandScan4.30 software.Results:The ratio of STK15 /GAPDH in the RT-PCR was 1.5839 (EJ), 1.4096 (5637), 1.3148 (T24), 0(normal bladder tissue), respectively. The ratio of STK15 /GAPDH in the Westem blotting was 5.13(EJ), 3.96(5637) and 1.5(T24), respectively. Compared with the normal bladder tissues, the expression of STK15 of mRNA and protein in all three bladder cancer lines was overexpressed,and the levels of STK15 were different: EJ＞5637＞T24.Conclusion: STK15 is overexpressed in three bladder carcinoma cell lines, and the levels of STK15 of mRNA and protein expression are different: EJ＞5637＞T24. PartⅡStudy on Expression of STK15 in Tissue of Bladder Transitional Cell Carcinoma and Its Clinical SignificancesObjective: In this part we want to acquire the expression of STK15 mRNA and protein in bladder transitional cell carcinoma (BTCC) tissue and normal bladder epithelial tissue. At the same time we want to know whether STK15 protein expression have relationship with the biological behaviors of BTCC. We can understand the molecular mechanism of BTCC all the better from these expression.Methods: STK15 mRNA was investigated using RT-PCR analysis in fresh bladder tumor tissues and normal bladder mucosa. Immunohistochemistry was used to detect the expression of STK15 in BTCC (n=40) and normal bladder mucosa (n=10); Immunohistochemistry results were analysised and the expression result was indicated by integrated optical density (IOD).Results: RT-PCR indicated that the expression level of STK15 in BTCC (n=40) was 100% and in normal bladder mucosa (n=10) was 0. Immunohistochemistry indicated that the IOD of STK15 in BTCC was significantly higher than normal bladder mucosa (P＜0.01). The expression level of STK15 was strongly correlative with pathological grade and clinical stage (P＜0.01). Conclusion: Result indicate that STK15 was the diagnostic and prognostic index of BTCC, and it provid theory basis about the gene target therapy in BTCC.PartⅢAssociation between genetic polymorphism in STK15 and risk of bladder cancer in a Chinese populationObjective: This study was designed to detect the association between STK15 Phe31 Ile polymorphism and bladder cancer.Methods: Genotypes were determined in 53 patients with bladder cancer and 30 controls. The adjusted odds ratios (ORs) and 95% confidence intervals(CIs) were calculated.Results: The frequency of the STK15 Ile/Ile genotype was significantly higher in cancer cases than in controls(28.30％vs. 13.33％; P＜0.01). Subjects with the Ile/Ile genotype had an increased risk for the occurrence of STK15 cancer compared with those with the STK15 Phe/Phe genotype(adjusted OR, 5.31; 95％CI, 1.06-9.56).Conclusion: These findings suggest-that STK15 Phe/Ile polymorphism may be a genetic susceptibility factor for bladder cancer among Chinese.