摘要
Abstract
Objective Bioinformatics analysis was performed to screen neuroinflammation-related hub genes and construct a prognostic model in estrogen receptor(ER)-positive breast cancer,exploring potential therapeutic targets for ER-positive breast cancer and screening targeted drugs.Methods The data of 840 ER-positive breast cancer and normal control samples were obtained from The Cancer Genome Atlas(TCGA)database for differentially expressed gene analysis.Combined with neuroinflammation-related genes retrieved from the GeneCards database,overlapping genes between neuroinflammation genes and differentially expressed genes(DEGs)were screened.Immune infiltration analysis,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on these overlapping genes to explore their biological functions.A multivariate COX regression model was used to construct a prognostic prediction model,and its predictive efficiency was validated.The potential microRNA(miRNA)regulatory network of key genes was analyzed,and candidate therapeutic drugs were predicted via the Comparative Toxicogenomics Database(CTD).Results A total of 2,529 DEGs were identified,including 1,383 upregulated genes and 1,146 downregulated genes.One hundred overlapping genes associated with neuroinflammation in ER-positive breast cancer were obtained.These overlapping genes were significantly enriched in cancer-related signaling pathways,homeostasis,immune and inflammatory responses,participating in diverse biological processes,cellular components and molecular functions.Immune infiltration analysis revealed altered abundances of multiple immune cells.Eleven genes related to the prognosis of patients with ER-positive breast cancer were screened out.The risk score prognostic prediction model constructed based on these 11 prognostic-related genes exhibited favorable predictive efficiency(3-year AUC=0.77,95%CI[0.67,0.88];5-year AUC=0.80,95%CI[0.72,0.87]).The 11 prognostic-related genes were regulated by 153 miRNAs and 43 transcription factors.Compounds interacting with overlapping genes were screened via the CTD database,and 29 candidate agents such as doxorubicin and resveratrol were predicted as potential therapeutic drugs.Conclusion Neuroinflammation‑related genes participate in the progression of ER‑positive breast cancer by regulating inflammatory pathways and remodeling the immune microenvironment.A total of 11 prognosis‑related genes were screened,and the prognostic prediction model constructed based on these genes exhibited favorable predictive value.Doxorubicin is a widely used clinical chemotherapeutic agent,while the anti‑inflammatory properties of resveratrol provide novel insights for combined therapeutic strategies.关键词
雌激素受体阳性乳腺癌/神经炎症/生物信息学/预后模型/枢纽基因Key words
Estrogen receptor-positive breast cancer/Neuroinflammation/Bioinformatics/Prognostic model/Hub genes
