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Effects Of ALDH5A1 On Ovarian Cancer Cells And The Relationship Between ALDH5A1 And The Prognosis Of Patients With Ovarian Serous Carcinomas

Posted on:2018-09-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:X TianFull Text:PDF
GTID:1314330515983415Subject:Obstetrics and gynecology
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Object:The aim of this study was to explore the relationship between ALDH5 A1 and the prognosis of patients with ovarian cancer(OC).Methods:We compared the expression of ALDH5A1 in OC to that in normal controls,using GSE40595 profiling data and CSIOVDB data.Tissue microarray analysis was conducted for 192 OC patients,14 adjacent normal ovary tissues,and 2 normal ovary tissues.Using the "Kaplan-Meier plotter"(KM plotter)database,updated gene expression data and survival information of a total of 1583 OC patients were used to evaluate the prognostic value of ALDH5A1 in OC patients.Results:We found that ALDH5A1 mRNA expression was downregulated in OC patients compared to that in normal tissues.In survival analyses,we found that ALDH5A1 was positively linked to prognosis in patients with OC,particularly in those with serous ovarian cancer(SOC).In addition,high transcription activity of ALDH5A1 was correlated with better overall survival in SOC patients expressing mutated TP53,but not in those expressing wild-type TP53.In pathological grades II/III,a high mRNA level of ALDH5A1 was associated with improved overall survival.The positive association between ALDH5A1 and prognosis was found not only in early stages(I and II),but also in advanced stages(? and ?)of SOC patients.Conclusions:results indicate that ALDH5A1 is an excellent predictive factor of OC and may play crucial roles in OC progression.Object:The aim of this study was to investigate the roles of ALDH5A1 expression on biological behavior of OC.Methods:CSIOVDB database was used to assess the correlation of EMT score and ALDH5A1 mRNA.Silencing the expression of ALDH5A1 in SKOV3 cell and prima ovarian cancer cell(POC)using CRISPR/Cas9(clustered regularly interspaced short palindromic repeasts/Cas9 nuclease)technology.and the cells were detected with RT-PC and Westernblot for verifying the inhibited effect of ALDH5A1,cck-8 was used to monitor cell proliferation,the cell adhesion was tested by cell adhesion assay,scratch assay was employed to evaluate the migration of the cancer cell.the cell invasion were tested by transwell,and CCLE database was used to assess the correlation of ALDH5A1 mRNA and cisplatin IC50 in OC cells.Results:We found that a low mRNA level of ALDH5A1 was associated with improved EMT.Both cell invasion and scratch assays indicated the the silence of ALDH5A1 could reduce the invasion and migration power of OC cells,the result of cck8 show the proliferation of OC cells were inhibited by ALDH5A1 silence,and we found that ALDH5A1 was positively linked to cisplatin IC50.Conclusions:results indicate that ALDH5A1 is an excellent predictive factor of OC and may play crucial roles in OC progression.
Keywords/Search Tags:Aldehyde dehydrogenase 5 family, member A1, prognosis, ovarian cancer, Kaplan-Meier plotter, biomarker, EMT, CRISPR/Cas9, invasion
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