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The Expression And The Clinical Significance Of Autophagy-related Gene ARHI And Beclin1in Endometrial Adenocarcinoma Tissues

Posted on:2014-02-22Degree:MasterType:Thesis
Country:ChinaCandidate:C P QuFull Text:PDF
GTID:2234330395996411Subject:Clinical Medicine
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Background:In recent years, to evaluate the relationship between autophagy andtumor has become a hot spot. The Cells autophagy is a fairly complexprocess which is also a biological process strictly regulated by a series ofrelated genes. The abnormal regulation of autophagy is closely related tothe occurrence and development of tumor. As the autophagy-related genes,Beclin1and ARHI are considered as the important role in the regulation ofautophagosome formation. Beclin1as the specific gene is involved inautophagic process and is a necessary molecules in the formation ofautophagosome. The composited body formed by Beclin1and the type IIIof PI3K (phosphatidyl inositol3-kinase) raises APG protein andLC3,which promots the positioning of autophagy precursor and directlyinvolves in the formation of autophagosomes in this way. Similarly,ARHI is an important and necessary molecular to participate in theformation of autophagy;ARHI can promote the transformation fromLC3I to LC3II and the location to the surface of autophagosome vesiclemembrane. There by,ARHI plays an important role in participating theformation of autophagy and regulating the autophagy activity. It issuggested that ARHI and Beclin1may co-participate in the formation of autophagy by certain pathways, which may have an affect on autophagyactivity in tumor cells. Currently,The expression of Autophagy-relatedGene ARHI and Beclin1in endometrial adenocarcinoma tissues have notbeen reported. Whether ARHI and Beclin1co-participate in regulatingautophagy activity,especially in endometrial adenocarcinoma tissues alsohave not been reported.Objects:In this study,the writer not only examined both the ARHI andBeclin1expression in the endometrial adenocarcinoma, endometrialhyperplasia and the normal endometrium tissue, but also analysed thecorrelation between each other. It explores the functions and relationshipsof both parties during the occurrence and development of endometrialadenocarcinoma. Study on relationship between these two genes and theexpression of autophagy. The writer also made an analysis of endometrialadenocarcinoma tissues ARHI and Beclin1ecpression and relevancy ofclinical parameters. Finally, the writer revealed the clinical significanceof ARHI and Beclin1’s expression in the endometrial adenocarcinoma. Itis expected that this research can provide theoretical evidence for seekingan effective and new therapeutic target and approaches.Materials and methods:The endometrium tissue samples from109cases included18cases ofnormal endometrium tissue,24cases of endometrial hyperplasia,67cases of endometrial adenocarcinoma (34cases of high pathohistologic grading,33cases of middle and cases of low pathohistologic grading). Accordingto the criteria of the2009International Federation of Gynecology andobstetrics (FIGO): clinical staging was divided into stage I (31cases),stage II (15cases), stage III and IV(21cases).In the second hospital ofJilin University, Bethune medical, collected between September2011and September2012. The age of the patients ranged from33to72years,with a average age of53.58years. All patients were not treated withradiotherapy, chemiotherapy and immunotherapy before tissues werecollected. All tissues were diagnosed by two pathologists.Immunohistochemical expressions of All specimens of ARHI and Beclin1on tissues was analyzed. The dates were analyzed by statistical softwareSPSS19.0: Chi-square test and Fisher fidelity probabilistic methodand Spearman,s rank correlation were performed to compare differentlybetween the groups and relativity analysis respectively. p value less than0.05was considered significant difference.Results1、The positive expression rates of ARHI and Beclin1in normalendometrium were94.4%,94.4%; the positive percentages in endometrialhyperplasia were79.2%,70.8%, respectively, and41.8%,44.8%inendometrial carcinoma group. Generally, the positive expression rate ofARHI, Beclin1in the development of endometrial adenocarcinoma decreased, the difference were statistically significant.(χ2=21.537, p=0.000; χ2=16.304, p=0.000)。2、The expression level of ARHI and Beclin1were not related to age,cervical invasion (p>0.05). The expression of ARHI was related with thecellular differentiation degree (χ2=5.635, p=0.018) operation, pathologicalstage (χ2=6.781, p=0.034), muscular layer infiltration (χ2=7.608, p=0.006)and lymph node metastasis (χ2=6.504, p=0.011), Beclin1expression isassociated with the degree of differentiation of tumor cells (χ2=14.603,p=0.000).3、ARHI in endometrial carcinoma was positively correlated withBeclin1protein expression (r=0.375, p=0.002)Conclusions1、The protein expression’s down regulation of Autophagy-relatedgene ARHI and Beclin1in endometrial adenocarcinoma has the referenceto the grade of tumor cell differentiation, which suggest that thealterations of autophagy activity may be associated with the occurrence,development of endometrial adenocarcinoma. It provides a basis for thetarget in the treatment of endometrial adenocarcinoma and newtherapeutic strategies.2、The Positive correlation showed on the expression of ARHI andBeclin1in endometrial adenocarcinoma suggests that the commonexpression of both parties in endometrial adenocarcinoma tissues may have a common regulatory mechanism.
Keywords/Search Tags:ARHI, Beclin1, autophagy, endometrial adenocarcinoma
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