Triple-Negative Breast Cancer-Associated Differentially Expressed Genes And Their Association With Prognosis

The incidence of breast cancer is currently the first in the incidence of malignant tumors in women,and the pathogenesis of breast cancer is complex and the prognosis is different.Triple negative breast cancer(TNBC)is a subtype of breast cancer defined according to immunohistochemical results,due to its heterogeneity and aggressiveness,resulting in a high degree of malignancy,a higher rate of distant metastasis than other subtypes,and a poor prognosis compared with other subtypes due to the lack of effective therapeutic targets,which has become a problem in the field of breast cancer treatment.In recent years,through the analysis of TNBC genes or others,a considerable number of drugs that are considered to be targeted therapeutic targets have been found,but they have not been entered into the guidelines due to lack of clinical evidence.Bioinformatics analysis,referred to as bioinformation analysis,is the use of bioinformatics tools,methods and technologies to analyze and research life science data.Bioinformation analysis mainly includes two categories: one is quantitative and qualitative analysis of DNA,RNA,proteins and metabolites,including tumor genome mapping(TCGA),gene expression synthesis(GEO),etc.The other is the graphical display,visual analysis and machine learning application of complex biological information data,which involves information technology operations such as R language.This article aims to study the genes associated with triple-negative breast cancer(TNBC)and their relationship with prognosis through bioinformation analysis.It is hoped that new targets can be found to provide new treatment options for targeted therapy of TNBC.Objectives: 1.To identify the differential genes of triple negative breast cancer(TNBC)and non-TNBC,and to find the enrichment analysis characteristics and pathways of upregulated genes.2.Analyzing the relationship between differential genes and the prognostic of TNBC,and exploring the new tumor markers for TNBC targeted therapy.Methods: The gene expression profiles of GSE76275 were downloaded from the Gene Expression Omnibus(GEO)dataset.The microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and198 TNBC.The differentially expressed genes(DEGs)of TNBC and non-TNBC were processed online through the limma packets of R language,and the characteristics and pathways of upregulated genes were studied by GO and KEGG enrichment analysis。The Cancer Genome Atlas(TCGA)was used to collect clinical data,and the correlation about up-regulated gene-related TNBC samples or patient.These genes and TNBC prognosis was studied by univariate and multivariate COX analysis.Results: There were 301 DEGs between TNBC and non-TNBC,including 110 upregulated genes and 191 downregulated genes(p<0.05,log FC absolute value > 1).The results of GO enrichment analysis about upregulated DEGs showed that for cellular components,upregulated DEGs were significantly enriched in chromosomes,kinetochore and intermediate filaments.For molecular functions,upregulated DEGs were significantly enriched with transcriptional co-regulatory activity,structural constituents of cytoskeleton,growth factor activity,serine-type peptidase activity,serine hydrolase activity,core promoter sequence-specific DNA binding,DNA replication origin binding,RNA polymerase II core promoter sequence-specific DNA binding,etc.For biological processes,upregulated DEGs were significantly enriched in epithelial cell differentiation,growth and development.KEGG analysis showed that genes are mainly involved in estrogen signaling pathway,Wnt signaling pathway and cell cycle.COX analysis showed that the gene mainly associated with TNBC prognosis was KRT6 A.Conclusions: 1.The genes between TNBC and non-TNBC are differential,and the aggregation is good.2.Up-regulation of differential genes is associated with TNBC heterogeneity,aggressiveness,and drug resistance,and participates in estrogen signaling pathway,Wnt signaling pathway and cell cycle.3.KRT6 A is a risk factor for TNBC prognosis and can become a new target for predicting TNBC prognosis and treating TNBC breast cancer.4.KRT6 A involve 3 upregulation pathways,including glycolysis gluconeogenesis,tight junction,and dorsoventral axis formation.The down-regulation pathways were the ABC transporters,glycine serine and threonine metabolism,protein export,fatty acid metabolism,vasopressin-regulated water reabsorption pathway,and glyoxylate and dicarboxylate metabolism.5.The expression of KRT6 A is no significant difference in the triple-negative breast cancer subspecies of the four Fudan classifications...