Screening Of Prognostic Related Genes In Partial Three-Negative Breast Cancer Based On GEO Database

Background and PurposeTriple negative breast cancer(TNBC)is a special type of breast cancer,accounting for 15-20% of all breast cancer cases.Because of its lack of estrogen receptor and progesterone receptor and low expression level of HER2,it is insensitive to hormones and targeted therapy,and the treatment method is almost only chemotherapy.In addition,because of the pathological classification of triple-negative breast cancer,invasive ductal carcinoma is common,and most patients with triple-negative breast cancer have a histological grade of grade 3 or above,and triple-negative breast cancer is the most intractable type of breast cancer.The purpose of this study is to find out the gene expression microarray data of triple-negative breast cancer and normal breast tissue by GEO database,and analyze it by bioinformatics,so as to find out the key genes related to triple-negative breast cancer and find possible therapeutic targets for triple-negative breast cancer..MethodThe gene chip data of triple-negative breast cancer and normal breast tissue were searched in GEO database,and the data sets that meet the research needs were screened out,namely GSE38959,GSE45827 and GSE65216(GPL570 platform).The three data sets were grouped and analyzed by using GEO2 R tool,and the volcano map was made.The three data sets were downloaded and the common difference genes of three groups of different genes were obtained by using the website of drawing Wayne map.The differential genes were introduced into David website for GO enrichment and KEGG signal pathway analysis,and the biological process(BP),cell composition(CC),molecular function(MF)and signal pathway information of differential gene expression products were obtained,and the bubble diagram was made by using Image GP.The protein-protein interaction network of different genes is constructed by using String database,and the results of the protein-protein interaction network are imported into Cytoscape software for visual mapping,and the core genes are obtained by using MCODE plug-in analysis.Finally,by using Kaplan-Meier Plotter database website,the survival and prognosis of patients with TNBC were analyzed,and the genes that have an impact on the survival and prognosis of patients with TNBC were screened out.ResultThree groups of gene chips downloaded from GEO database were screened according to the conditions(|log2FC|>3,adj.P<0.01),and 135 genes with different expression were obtained by using the intersection of Wayne Diagram websites.Among these 135 genes,85 genes were up-regulated and 50 genes were down-regulated.The obtained differential genes were analyzed by GO enrichment and KEGG pathway respectively.The results showed that the biological processes(BP)in which differential genes participated were cell division,cell cycle,chromosome separation,mitotic cell cycle,positive regulation of cell proliferation,apoptosis,protein phosphorylation,mitotic spindle assembly checkpoint,mitotic sister chromatid separation and so on.Cell components(CC)mainly include: nucleus,cytoplasm,nucleoplasm,cytosol,intermediates,centromeres,centrosomes and so on.Molecular functions(MF)mainly include protein binding,adenosine triphosphate binding,microtubule binding,DNA binding,protein kinase binding,chromatin binding and so on.KEGG signaling pathway analysis showed that the pathways involved by differential genes mainly focused on Cell cycle,Pathways in cancer,p53 signaling pathway and so on.Protein-protein interaction network(PPI)analysis of differential genes was carried out by the tool of STRING online database,and 38 core genes were identified by MCODE,a plug-in of Cytoscape.The survival and prognosis of these core genes were analyzed on Kaplan-Meier Plotter database website.The results showed that the expression of eight genes,namely ASPM,CDCA2,CENPF,KIF20 A,NDC80,PBK,PTTG1 and TPX2,was closely related to the prognosis of TNBC.The specific results are as follows: in triple negative breast cancer,the total survival time of the eight core genes,ASPM,CDCA2,CENPF,KIF20 A,NDC80,PBK,PTTG1 and TPX2,is longer in the high expression group than in the low expression group(the follow-up time is10 years),and the p values are 0.012,0.0088,0.032,0.037,respectively.There was no significant difference in the overall survival time between the high-expression and low-expression groups of the other 30 core genes(P>0.05).Conclusion1.Compared with normal breast tissue,The core expression genes in triple negative breast cancer tissues are ZWINT,CENPN,CDK1,KIF11,KIF20 A,PBK,TTK,DTL,ANLN,KIF23,HMMR,RRM2,CDC45,CENPF,OIP5,MELK,CCNA2,TOP2 A,BUB1,CDC6,TPX2.ASPM、BIRC5、NDC80、KIAA0101、CDCA8、PRC1、CDCA2、DEPDC1、NUF2、SPAG5、NUSAP1、BUB1B、CDKN3、PTTG1;2.ASPM,CDCA2,CENPF,KIF20 A,NDC80,PBK,PTTG1 and TPX2 are related to the survival and prognosis of triple negative breast cancer patients,showing that the total survival time of the high expression group is prolonged(the follow-up time is 10 years),and the P values are all less than 0.05,which is statistically significant.3.Eight key genes,such as ASPM,CDCA2,CENPF,KIF20 A,NDC80,PBK,PTTG1 and TPX2,are related to the survival and prognosis of patients with triple negative breast cancer,and may become potential therapeutic targets.