Study On The Correlation Between The Variable Shear Event Characteristics Of Breast Cancer And The Prognosis And Immune Microenvironment

Objective:Alternative shearing(AS)has become a key factor in tumor development and microenvironment formation.There is an urgent need for a comprehensive analysis of the AS events and to explore its clinical significance in breast cancer(Breast Cancer,BrCa).Methods:In this study,the Cancer Genome Atlas(TCGA)data from993 BrCa patients was used for genome-wide analysis of AS events via RNA Sequencing(RNA-Seq).Then,the differentially expressed alternative splicing(DEAS)events were identified between BrCa tissue and normal tissue adjacent to the cancer,and the functional enrichment analysis of the DEAS events were performed.At the same time,bioinformatics tools were used to construct the DEAS events' parent gene interaction network,splicing network and splicing regulation network.Based on the overall survival(Overall Survival,OS)and disease-free survival(DFS),the proportional hazard regression model(proportional hazards model,Cox model)method was used to sift independent prognostic risk factors.In addition,the possible molecular typing of BrCa based on independent prognostic risk factors was explored,and the correlation between typing and clinical,molecular,and immune characteristics was analyzed.Results: Finally 35,520 AS events in BrCa were detected and 678 DEAS events were identified.Parent genes of DEAS events are significantly enriched in pathways related to BrCa and tumor immune microenvironment,such as cancer pathway(FDR = 0.001),MAPK signaling pathway(FDR = 0.001),ECM-receptor interaction(FDR =0.004),PI3K-Akt signaling pathway(FDR= 0.005).The AS-SF regulatory network indicates that there is a significant correlation between the expression of Splicing Factor(SF)and the DEAS event.The stepwise Cox regression analysis showed that 13 and 10 AS events were respectively independent prognostic factors for OS and DFS.Unsupervised cluster analysis shows that there is a clear correlation between AS-based clustering and prognosis,molecular characteristics and immune characteristics.Meanwhile,it was found that high levels of CD8+ T cells and NK cells are associated with a better prognosis.Conclusions:AS events based on independent prognostic factors revealed the inherent correlation between molecular changes and immune characteristics in BrCa unsupervised cluster analysis.The cluster1 subtype has a high content of CD8 + T cells and NK cells and is associated with a better prognosis.