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Quantitative Proteomics Analysis Of Different Pathogenesis Of Renal Clear Cell Carcinoma And Chromophobe Renal Cell Carcinoma

Posted on:2018-01-02Degree:MasterType:Thesis
Country:ChinaCandidate:G D LuoFull Text:PDF
GTID:2334330518451861Subject:Urology
Abstract/Summary:PDF Full Text Request
Background: Renal tumor is the most common adult kidney tumor. Early renal tumor after 5 years of treatment can be as high as 89% survival rate, but because of lack of specific symptoms,signs and laboratory tests,more than 30% of renal tumor diagnosis has reached the advanced stage, 5-year survival rate is less than 5 %. Renal clear cell carcinoma is a kind of moderate malignant potential tumor, which accounts for more than 85% of the type of renal tumor, originated in the renal tubular epithelial cells.Chromophobe renal cell carcinoma is a kind of low malignant potential tumor, derived from renal tubular cells with good prognosis and unique ultrastructure and genetic characteristics. The incidence rate behind clear renal cell carcinoma and papillary adenocarcinoma, accounting for about 3.2%. Clinically, clear renal cell carcinoma and Chromophobe renal cell carcinoma are lack of specific imaging performance,preoperative diagnosis has some difficulties, postoperative pathology is necessary. The proteomics technology with the gene chip technology compared with high-throughput,high sensitivity and high precision and other advantages, distinguish between different types of renal tumor has some advantages. And renal tumor molecular targeted drugs such as sorafenib, sunitinib, sirolimus, everolimus and other clinical treatment has begun to take effect, so the use of proteomics to find available early diagnosis for renal tumor and treatment of tumor markers have a certain practical significance.Methods: Use TMT quantitative proteomics to analyze 5 early clear renal cell carcinoma patients and 5 chromophobe renal carcinoma patients, landing GO and KEGG database to identify proteins by bioinformatic and pathway analysis. Select differences expression proteins through different expression and bioinformatics analysis combined with literature review, choose those proteins which are related with progression, signal transduction pathways and associated with the invasion and metastasis of clear renal cell carcinoma samples and chromophobe renal carcinoma sample. Using Western blot technique on one of two different proteins for validation.Finally, use statistical software SPSS 18.0 with t test and Kaplan-Meier survival analysis,analysis of the relationship between the expression of two different proteins in patients with gastric cancer recurrence and metastasis and its influence on the prognosis.Results : With TMT quantitative proteomics method to obtain a total of 400 differentially expressed proteins identified (101 up-regulated and 299 down-regulated).Login GO database search found differences in protein mainly located in the cell cytoplasm, organelles and cell membrane, and so on. Its function associated with binding, catalysis, enzyme regulation. Physiological and pathophysiological processes are involved in signal transduction pathways, metabolism, single-cell biological processes, antioxidant, adjusting channels, and so on. Login KEGG pathway database searches found differences in protein mainly located in oxidation reduction, cellular respiration, oxidative phosphorylation and generation of precursor metabolites and energy. Login String database searches found PYGL and PYGB are the key differentially expressed proteins. Western blot showed that PYGL protein expression in ccRCC serum higher than Para tumor serum expression, chRCC serum were lower than Para tumor serum expression, but PYGB in ccRCC serum was not significant changed,in chRCC serum were higher than Para tumor serum expression, the differences were statistically significant (P<0.05).Conclusion : Our research use TMT quantitative proteomics technology initially screened the differences protein in serum of ccRCC and chRCC, found a total of 400 different proteins. We screened out two key proteins which have good diagnostic value:PYGL and PYGB, We verify two different proteins by western blot. We found PYGL protein expression in ccRCC serum higher than Para tumor serum expression, chRCC serum were lower than Para tumor serum expression. however, the sample size may still need to further expand in the next study.
Keywords/Search Tags:renal tumor, clear renal cell carcinoma, chromophobe renal cell carcinoma, TMT, LC-MS/MS
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