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Comparison Of Breast Ductal Carcinoma In Situ,Microinvasive And T1 Invasive Carcinoma And Forecasting Model Research

Posted on:2023-06-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:R R ZhuFull Text:PDF
GTID:1524307025484154Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objectives1.To explore predictive value of preoperative combined detection of peripheral blood indicators for the invasion of DCIS,DCIS-MI and T1a-c IDC,and construct and evaluat the prediction model which was based on peripheral blood indicators.2.To discuss the clinicopathological characteristics of DCIS,DCIS-MI and T1a-c IDC,and construct and evaluat the prediction model which was based on clinicopathological data and cone-beam breast CT(CBBCT)imaging findings.3.To search for key genes related to invasion and metastasis of breast ductal carcinoma,which was based on Gene Expression Omnibus(GEO)database,so as to provide a new research direction for further exploring the occurrence,development and metastasis of ductal carcinoma.4.To verify the difference in expressions of the differential gene-related protein MMP-1 in breast hyperplasia tissues,pure intraductal carcinoma of breast tissues,pure invasive carcinoma of breast and IDC-DCIS paraffin-embedded tissues by immunohistochemical method,and to explore its clinical significance in breast tumor invasion and metastasis.Methods1.Collected relevant information.According to whether there is infiltration in patients with ductal carcinoma,combined with preoperative blood routine and clinicopathological data,the predictive value of preoperative blood routine parameters on the infiltration of ductal carcinoma of breast was investigated.Chi-square test and U test were used for single factor analysis to screen out indicators with statistically significant differences.The indexes such as neutrophil/monocyte ratio were substituted into binary logistics regression analysis,and the prediction model was constructed.The patient information of the validation group was substituted into the model to calculate the risk value and verify its accuracy.Then,the ROC curve of the predictors was made with the presence of infiltration as the dependent variable,and the optimal truncation value was calculated.Patients were re-divided into the high level group and the low level group according to the cut-off value,and the differences between the two groups were compared.2.The clinical pathology and CBBCT indexes were compared among DCIS,DCIS-MI and IDC groups.The clinical,pathological and CBBCT differences of the three groups were compared,and the model for predicting the occurrence and infiltration of ductal carcinoma was established by using relevant indicators,and the model was verified.Chi-square test,U test,binary logistics regression analysis,ROC curve and other statistical methods were used in the study.3.Download data through the Gene Expression Database(GEO)of the National Center for Biotechnology Information(NCBI),use bioinformatics software to mine differentially expressed genes,and analyze them through DAVID,STRING and other online tools for GO enrichment analysis,KEGG pathway Analysis and protein interaction(PPI)analysis,finally obtained the Hub gene by Cytoscape software,and then used the Kaplan-Meier online tool to obtain the Hub gene-related survival curve.4.The immunohistochemical En Vion method was used to verify the expression difference of MMP-1 protein in normal breast tissue,pure DCIS tissue,pure IDC tissue and IDCS-DCIS tissue,and to explore the significance of MMP-1 in the infiltration of ductal carcinoma.Results1.For patients with early-stage breast ductal carcinoma,preoperative peripheral blood NMR,age,and history of abortion are independent predictors of breast ductal carcinoma invasion.The age of onset of the patients in the DCIS group was younger than that of the patients in the invasive cancer group,and the proportion of postmenopausal patients was also significantly lower than that of the patients in the invasive cancer group.Best cutoff value for preoperative NMR: 12.35.The ratio of L-NMR DCIS group(33/59)was significantly lower than that in IDC group(72/84).2.The expression of Ki67 in DCIS-MI and DCIS was higher than that in DCIS,and the difference of other indexes was not significant.There were significant differences in clinicopathological and CBBCT findings between DCIS-MI and IDC.ER,pathological calcification,and tumor type are independent predictors of breast ductal carcinoma invasion.The model could better improve disease diagnosis rates.3.A total of 171 differentially expressed genes were obtained,including 62up-regulated genes and 109 down-regulated genes.Analysis indicated that these genes were mainly related to biological processes such as cell division and mitosis,and were closely related to the occurrence and development of breast cancer.A total of 18 Hub genes were predicted to be obtained.4.MMP-1 expression was significantly different in breast hyperplasia tissues,pure intraductal carcinoma,pure invasive ductal carcinoma and IDC-DCIS(P=0.003).Regardless of the source of ductal carcinoma,MMP-1expression was higher in pure invasive ductal carcinoma and IDC of IDC-DCIS than in pure DCIS and DCIS of IDC-DCIS(P<0.05).The expression of MMP-1in ductal carcinoma of breast was not related to the clinicopathological parameters of breast cancer(P>0.05).Conclusions1.The peripheral blood prediction model has certain evaluation and prediction value for the occurrence of invasion in early breast cancer.Preoperative peripheral blood NMR,age,and history of abortion are independent predictors of invasion in ductal breast cancer.The optimal cut-off value of NMR was 12.35.2.CBBCT prediction model has certain evaluation and prediction value for the occurrence of T1a-c invasion ductal cancer.DCIS-MI has similar clinicopathological imaging features with DCIS except Ki67,but differs from IDC clinicopathological imaging.3.About 171 DEGs and 18 Hub genes that may be involved in the occurrence and development of breast ductal carcinoma were screened.DEGs are involved in biological processes such as cell division and mitosis.The two genes with the highest score in Hub genes,KIF20 A CCNA2,both play an important role in the process of mitosis and can be used as predictors of breast cancer,both of which are related to tumor invasion.4.MMP-1 expression was different in breast hyperplasia tissues,pure intraductal carcinoma,pure invasive ductal carcinoma and IDC-DCIS.Regardless of tumor cell origin,MMP-1 expression in IDC was higher than that in DCIS.The expression of MMP-1 in ductal carcinoma of breast was not related to the clinicopathological parameters of breast cancer.
Keywords/Search Tags:invasive ductal carcinoma, ductal carcinoma in situ, inflammatory markers, prediction model, matrix metalloproteinase-1
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