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Effects Of PLAC8 On The Renal Clear Cell Carcinoma Cells And Its Effect Mechanism Research

Posted on:2018-03-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:L P ShiFull Text:PDF
GTID:1314330536983722Subject:Surgery
Abstract/Summary:PDF Full Text Request
Renal cell carcinoma(RCC)is one of the most common malignancies in the adult urinary system.The incidence rate is slightly lower than that of bladder cancer,accounting for 90%-95% of all renal malignancies.Renal cell carcinoma mainly includes three types of pathology,in which clear cell renal cell carcinoma(ccRCC)is the highest pathologic type,accounting for 65% of all reported cases,followed by papillary renal cell carcinoma(pRCC)and chromophobe cancer,each accounting for 15% to 20% and 5% respectively.In recent years,the incidence of renal cell carcinoma showed an increasing trend year by year.More than half of the early onset of renal cell carcinoma without obvious symptoms,more than 17% of renal cell carcinoma diagnosis has been distant metastasis.The renal cell carcinoma which has a distant metastasis 5-year survival rate is less than 10%,the median survival time is less than one yearAt present,surgery is still the best treatment of renal cell carcinoma,for the presence of distant metastasis of renal cell carcinoma patients,cell immunotherapy and tumor targeting drug therapy has been more and more applications.There is no effective clinical treatment for patients with recurrence of renal clear cell carcinoma after surgical treatment.Therefore,to study the specific mechanism of renal clear cell carcinoma has great significance,which can improve the diagnosis and treatment of renal clear cell carcinoma.Placenta specific 8(PLAC8),formerly known as onzin,is a protein rich in cysteine,first found in human placental tissue.PLAC8 is widely distributed in the human immune system and a variety of tissue epithelial cells,PLAC8 can regulate cell division,differentiation and apoptosis,and the human body is closely related to the occurrence of a variety of tumors.But its role in renal cell carcinoma has not been reported.The main goal of this paper is to study the role of PLAC8 in the development and progression of renal clear cell carcinoma and its possible mechanism.This paper is divided into four parts.In the first part,the expression of PLAC8 in renal clear cell carcinoma and adjacent tissues was analyzed by Real-Time PCR and immunohistochemistry.The expression of PLAC8 protein and mRNA in renal clear cell carcinoma was higher than that in normal renal tissue.In the second part,the relationship between the expression of PLAC8 and the clinical prognosis of renal clear cell carcinoma was analyzed by the clinical data of renal clear cell carcinoma.The expression of PLAC8 is related to the progression and prognosis of renal clear cell carcinoma.The expression of PLAC8 can be used as a marker for survival prognosis of renal clear cell.The third part mainly studies the effect of PLAC8 expression on the biological behavior of renal clear cell carcinoma cells.The decrease of PLAC8 expression in renal clear cell carcinoma cells can decrease the ability of invasion and proliferation of renal clear cell carcinoma cells and inhibit cell viability,And increase the sensitivity of renal clear cell carcinoma to chemotherapeutic drugs(cisplatin),increase the cytotoxicity of chemotherapeutic drugs(cisplatin)to cancer cells.In the fourth part,we discussed the possible mechanism of PLAC8 affecting the biological behavior of renal clear cell carcinoma cells.By RNA-seq analysis,we found that there were 697 PLAC8 down-regulated genes and 829 up-regulated genes.By GO and KEGG pathway analysis,we found that response to stimulus,response to chemicals and immune system process were among the top 3 biological processes,PLAC8 may play an important role in regulation of the ccRCC inflammatory microenvironment.
Keywords/Search Tags:placental specific protein 8, renal clear cell carcinoma, cell proliferation, cell invasion, RNA interference, prognosis, pathway
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