Data screening and bioinformatics analysis for targeted therapy in estrogen receptor positive breast cancer
Objective To screen the library data of clustered regularly interspaced short palindromic repeat(CRISPR)for predicting new therapeutic targets in estrogen receptor(ER)positive breast cancer.Methods CRISPR library sequencing data and expression profile chip data were retrieved to compare tamoxifen resistance among different groups of ER-positive breast cancer cells,focusing on the deletion target genes and differentially expressed genes.The gene lists from sequencing and expression profive chip data were intersected.The protein-protein interaction networks(PPI)of potential tamoxifen resistant genes were analyzed using the data visualization software.Gene function and pathways were annotated using the database for annotation,visualization,and integrated discovery.Core gene sets were analyzed using the software for gene set enrichment analysis(GSEA),with intersections between three core gene set and the potential tamoxifen resistant gene.Survival curves were plotted using the database of gene expression profiling interactive analysis.qRT-PCR and immunohistochemical(IHC)experiments were conducted to determine basigin(BSG)expression levels in ER-positive breast cancer patients.Results CRISPR library sequencing data and expression profile chip data screened out 61 potential tamoxifen resistance genes,and PPI analysis revealed that 30 genes exhibited significant interactions.Intersection analysis between the 30 genes and three core gene sets from GSEA identified BSG as the sole gene present.Survival analysis demonstrated a correlation between high BSG expression and poor disease-free survival in patients(P＜0.05).qRT-PCR and IHC experiments confirmed significantly higher BSG expression in ER-positive breast cancer patients.Conclusion Based on CRISPR library analysis,BSG is a promising predictive target for novel therapies in ER-positive breast cancer patients,and the prediction results have been further verified by biological function experiments and clinical findings.
Estrogen receptor positive breast neoplasmsTamoxifenDrug resistanceBasigin
万方数据
维普
