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The Correlation Between The Expression Level Of YAP In Various Subtypes Of Breast Cancer And The Prognosisof Patients

Posted on:2021-04-22Degree:MasterType:Thesis
Country:ChinaCandidate:F L MengFull Text:PDF
GTID:2404330602984209Subject:Surgery
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Objective:The expression levels of YAP(YAP)in various subtypes of breast cancer were detected by bioinformatics technology and basic biological experiments,and its value in the diagnosis of various subtypes of breast cancer was compared and determined.By following up the survival information of patients,the correlation between YAP expression level and breast cancer stage,grade and prognosis was clarified.The successful completion of this project can provide a new therapeutic target for breast cancer,and the clinical transformation of this study provides a theoretical and scientific basis for accelerating the individualized diagnosis and treatment and comprehensive management of breast cancer.Methods:1.Register and log in the Oncomine database,download the breast cancer data set containing the transcriptome information of YAP that meets the requirements of the study,and analyze the relationship between the expression level of YAP and the clinical characteristics of breast cancer and the overall survival rate at the transcription level by using bioinformatics methods.At the same time,the differences in the expression levels of YAP in each subtype of breast cancer and its correlation with the prognosis of each subtype of breast cancer were analyzed at the transcription level.2.Twenty-one cases of each subtype of breast cancer and their corresponding para-cancer tissues(?2cm from the tumor boundary)were collected from the specimen library of the department of pathology,Yijishan hospital,and a patient information database was established.Immunohistochemical staining and Image J software IHC grayscale analysis were used to detect YAP expression levels in each sample,and statistical methods were further applied to analyze the differences in YAP expression levels in each molecular subtype of breast cancer and its correlation with the prognosis of each molecular subtype of breast cancer at the protein level.3.The survival information of patients from the sectioning source was followed up by telephone,and the survival analysis of patients was performed by Kaplan-Meier method.The influencing factors of YAP expression level were analyzed by binary Logistic regression.The correlation between the expression level of YAP in each subtype of breast cancer and the prognosis of patients and the influencing factors of YAP expression were comprehensively analyzed.Results:1.The expression of YAP in the database in normal breast tissues and breast cancer tissues was analyzed,and the expression level of YAP in breast cancer tissues was down-regulated.The meta-analysis results showed that p=2.23×10-5,and the difference was statistically significant.2.In the TCGA Brest data set,the mRNA expression value of YAP in breast cancer tissues was significantly lower than that in normal breast tissues,with statistically significant differences(t=2.189,p=0.0296).In breast cancer patients,the overall postoperative survival rate of patients with high YAP expression was significantly higher than that of patients with low YAP expression,with a statistical difference(p=0.0016).3.Compared with grade 1 histological grade,YAP expression level in breast cancer with grade 2 histological grade decreased,but there was no statistical difference(P>0.05),while YAP expression level in breast cancer with grade 3 histological grade decreased significantly(p=0.0005).Compared with breast cancer tissues with distant metastasis in 5 years after surgery,YAP expression level in breast cancer tissues without distant metastasis was low,and the difference between groups was statistically significant(p=0.0220).4.In the TCGA Brest data set,the mRNA transcription level of YAP in Luminal A type and her-2 overexpressed breast cancer was lower than that in normal breast tissue,but the difference was not statistically significant(p>0.05).The m RNA transcription level of Luminal B type and triple negative breast cancer tissues was significantly lower than that of normal breast tissues,with P values of 0.048 and 0.0285,respectively,and the difference was statistically significant.There was a statistical difference in the overall survival time of each molecular subtype of breast cancer(p<0.0001).Among the molecular subtypes of breast cancer,there was no significant difference in overall survival between patients with high expression of YAP and those with low expression of YAP in Luminal A and her-2 overexpression breast cancer(p>0.05).In Luminal B type and triple negative breast cancer tissues,the survival time of breast cancer patients with high YAP expression was significantly longer than those with low YAP expression,and the difference was statistically significant(p values were 0.0477 and 0.0366,respectively).5.The expression of YAP in various molecular subtypes of breast cancer was detected by immunohistochemical staining,and OD value was analyzed by Image J software.Compared with normal breast tissue,the average OD value of the immunohistochemical staining images of Luminal A type and HER-2 overexpressed breast cancer was lower,but there was no statistical difference(p>0.05).The mean OD values of Luminal B and triple negative breast cancer IHC images were significantly lower,and the results were statistically significant(p values were 0.0489 and 0.0053,respectively).6.There were significant differences in the overall survival of patients with various subtypes of breast cancer(p=0.0218).In Luminal A,Luminal B and HER-2overexpression adenocarcinomas,there was no significant difference in overall survival between patients with high expression of YAP and those with low expression of YAP(p>0.05).In triple negative breast cancer,compared with breast cancer patients with low YAP expression,the overall survival of breast cancer patients with high YAP expression was longer,and the results showed a statistical difference(p=0.0380).7.Binary logistic regression analysis showed that among 41 patients with high YAP expression,26(63.41%)were PR positive breast cancer patients.Among 43 patients with low YAP expression,7 patients with PR positive breast cancer(16.28%),and the difference in PR positive rate between patients with high YAP expression and patients with low YAP expression was statistically significant(?~2=19.550,p<0.005).Logistic regression model adjusted the histological grade,the probability of YAP overexpression in PR positive patients increased by 5.878 times(95%Cl:1.982?18.260)compared with PR negative patients.Conclusions:The expression levels of YAP in different breast cancer subtypes were different and correlated with some clinical characteristics of breast cancer.The influence of YAP on the prognosis of patients may depend on the level of PR expression.In Luminal B type and triple negative breast cancer,patients with low YAP expression of breast cancer tend to have worse prognosis.
Keywords/Search Tags:Breast cancer, YAP, Hippo signaling pathway, Prognosis
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