Screening For Potential Biomarkers And Therapeutic Agents For Lumina1 Breast Cancer Based On Gene Expression Profile

Objective:To screen potential biomarkers and therapeutic agents for lumina1 breast cancer based on gene express ion pro file and connectivity map.Methods:GSE42568,GSE45827 and GSE61304 which contain gene expression profiles of lumina1 breast cancer and normal breast tissue were downloaded from the GEO database.Significant differentially expressed genes(DEGs)were screened by R language and Bioconductor software,and pathway enrichment analysis of the identified DEGs was performed using Metascape.The Cytoscape software was used to construct a network map of significant DEGs encoding proteins to identify core gene populations.The TCGA database was used to verify the expression of the core gene cluster in lumina1 breast cancer patients and its relationship with clinical prognosis.Use the Connectivity Map database to screen for drug candidates that have a therapeutic effect on lumina1 breast cancer.The inhibitory effect of drug candidates on the proliferation of MCF-7 breast cancer cells was examined by MTT assay,and the effection on tumor cell cycle of the drug was analysed by Flow Cytometry.Results:A total of 375 significant DEGs were shared among the three datasets,of which 136 were up-regulated and 239 were down-regulated.And these genes were mainly enriched in PPAR,ECM receptor,AMPK,cell cycle,lipid degradation,and PI3K-Akt signaling pathways.Finally,a core gene group of 8 genes including CCNB1,CDK1,PBK,TOP2A,RACGAP1,CDC20,UBE2C,and MELK was screened.The expression of this core gene group in lumina1 breast cancer was significantly higher than that of normal population(P<0.05),and the survival rate of patients with low expression of core gene group was significantly higher than that of patients with high expression(P<0.05).Ten candidate therapeutic agents were screened,including celastrol,apigenin,chrysin and so on.Chrysin was confirmed to inhibit the proliferation of MCF-7 breast cancer cells,and it induced cell cycle arrest in G2 phase.Conclusions:The core gene group is expected to be a prognostic bio marker for lumina1 breast cancer.Connectivity map can be used to rapidly discover potential therapeutic agents for lumina1 breast cancer,and the blindness of drug development research can be reduced,which provides a research direction for the treatment of the disease.