Construction Of Gene Regulatory Network Of Immune Cells Highly Related To Autophagy In Breast Cancer And Its Dynamics Of Wnt Pathway Enrichment Under The Regulation Of Gene

Metastasis of breast cancer is the focus of prognosis treatment.The main cause of cancer patients’death is that cancer cells spread to other organs,and this process requires the participation of specific molecular features.Therefore,fully understanding these specific molecular features has the therapeutic potential to inhibit this fatal process.Studies have shown that autophagy inhibits the metastasis of breast cancer cells,that is,autophagy participates in the development of breast cancer.At the same time,Tumor microenvironment is the focus of tumor prognosis research in recent years,and many tumor immunotherapy drugs have been approved by FDA for clinical application.Therefore,it is urgent to find autophagy-related coding genes with prognostic value and realize personalized treatment for breast cancer patients.This paper identifies high-risk patients related to autophagy and looks for important immune cells related to autophagy by constructing autophagy-related prognosis model.In the second chapter,based on the theory of systems biology,an autophagy-related prognosis evaluation model was established according to 11 features screened by LASSO COX regression analysis.The model showed that the overall survival rate of patients in 1 year,3 years and 5 years was good,with AUC of 0.67 and 0.63 respectively.0.64.The model also significantly stratified the overall survival rate of patients clinically defined as stage Ⅱ/Ⅲ.In order to find important immune cells related to autophagy,this chapter used the algorithm of ESTIMATEARG and CIBERSORT.The result of ESTIMATEARG showed that the better the prognosis signal,the higher the immune score of the patient.The calculation result of CIBERSORT showed that among the four immune cells,there were significant differences in the abundance of dendritic cells(DC)among different autophagy risk groups.For identification,In the third chapter,the important genes of DCs are searched from plasma-like dendritic cells(pDC)and conventional dendritic cells(cDC),and the role of DCs in the treatment of breast cancer is evaluated.First,the cell abundance of 64 kinds of immune cells and stromal cells in tumor samples is calculated by xcell algorithm.Then,the gene module of co-expression of patients with high infiltration pDC and cDC is searched by weighted gene co-expression network analysis(WGCNA).Five hub genes were screened out.Finally,the effects of these hub genes and DC on breast cancer were revealed,and potential therapeutic strategies were provided for precise treatment of breast cancer.In this chapter,a pathway in which hub genes jointly participate in regulation-Wnt pathway was found.In the fourth chapter,the influence of BCL9 gene on Wnt signaling pathway is discussed.Based on Lee et al.’s model,the complex of GSK3B,APC and Axin is regarded as a whole,and 10 ordinary differential equation models are established considering the enhancement effect of BCL9 on the activity of β-catenin,and numerical simulation is carried out according to the existing literature.To reflect the effect of up-regulated BCL9 gene on beta-catenin and β-catenin on the binding of TCF.In this chapter,we also consider the different effects of the up-regulated BCL9 gene on the Wnt signaling pathway in the normal state and abnormal activation state.The results show that regardless of the mutation state of Wnt signaling components,BCL9 enhances the transcription activity mediated by β-catenin.This shows that the disorder of BCL9 gene is an important factor in tumor progress.