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The Analysis Of The N-WASP Dependent Mechanism Of Invasion And Metastasis Of Clear Cell Renal Cell Carcinoma And Correlation With Clinicopathological Features

Posted on:2016-06-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:J ChenFull Text:PDF
GTID:1224330461976645Subject:Urology
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Objectives:Compare the expression status of Cortactin, N-WASP and P-N-WASP in clear cell renal cell carcinoma and that in para-tumor tissue. Analyze the roll of Cortactin and N-WASP in N-WASP dependent mechanism of invasion and metastasis of clear cell renal cell carcinoma. Examine the expression status of N-WASP in clear cell renal cell carcinoma of different pathological grades and clinical stages. Examine the level of N-WASP expression in clear cell renal cell carcinoma and its association with clinicopathological features characteristic of this disease.Methods:Study 1Compare the difference of expression status of Cortactin, N-WASP and P-N-WASP between clear cell renal cell carcinoma and that in para-tumor tissue in 8 patient via immunohistochemical stain and western blot.Study 21. Seventy-three CCRCC patients who underwent radical nephrectomy were enrolled in this study. Immunohistochemical staining for N-WASP was performed on tissue microarrays constructed from tumor and para-tumor tissue obtained from these patients. The difference in N-WASP expression between tumor tissue and adjacent normal renal tissue was examined.2. Correlations between N-WASP expression in the tumor and clinicopathological parameters were analyzed and the relationship between N-WASP expression and overall survival also assessed. Univariate and multivariate survival analyses were performed using the Cox proportional hazards regression model.Results:Study 1Cortactin, N-WASP and P-N-WASP expression were significantly reduced in tumor tissues compared to para-tumor tissue.Study 21. N-WASP was significantly reduced in tumor tissues compared to para-tumor tissue.2. N-WASP expression level was significantly related to the histological grade of clear cell renal cell carcinoma.3. A higher level of N-WASP expression in the tumor was an indicator of poor survival in clear cell renal cell carcinoma patients. Patients with higher N-WASP expression levels have lower overall survival rate than patients with low or moderate N-WASP expression levels.4. Level of N-WASP expression, age at time of surgery (P=0.032), and histological grade were all responsible for clinical outcome in clear cell renal cell carcinoma patients.5. N-WASP was also an independent predictor for overall survival.Conclusions:Cortactin, N-WASP and P-N-WASP was significantly downregulated in CCRCC and could serve as a promising prognostic biomarker for predicting clinical outcome in patients with clear cell renal cell carcinoma.
Keywords/Search Tags:Clinicopathological
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