225Ac-DOTA-曲妥珠单抗对HER2阳性乳腺癌细胞基因表达的调控作用OA

OBJECTIVE:To investigate effect of 225Ac-DOTA-trastuzumab on gene expression profiles in HER2-positive breast cancer cells,and on mechanisms for proliferation inhibition of these cells.METHODS:HER2-positive breast cancer cells were divided into the model group,trastuzumab treatment group(test group),and 225Ac-DOTA-trastuzumab treatment group(analysis group).High-throughput transcriptome sequencing was performed to detect gene expression levels in each group.Differentially expressed genes(DEGs)were screened with the threshold of|log2(FC)|>1 and P<0.05.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used for functional enrichment analysis of DEGs to clarify their biological functions and effect on signaling pathways.Gene Set Enrichment Analysis(GSEA)was conducted to identify significantly enriched gene sets.Based on the screened DEGs,a protein-protein interaction(PPI)network was constructed to hub regulatory proteins.RESULTS:A total of 41 DEGs were identified between the test and the model groups,including 19 up-regulated and 22 down-regulated genes.In contrast,1323 DEGs were screened in the analysis group versus the model group,among which 703 genes were up-regulated,and 620 genes were down-regulated.Volcano plots and clustering heatmaps verified reliability of the differential expression results.GO enrichment analysis yielded 620 functional terms,mainly involving cell adhesion,inflammatory response and other biological processes.A total of 84 signaling pathways were enriched via KEGG analysis,which were closely associated with the occurrence,progression and signal transduction of breast cancer.Four core gene sets were screened by GSEA,and 30 hub interacting proteins were identified through the PPI network.CONCLUSION:This study identified differential gene expression patterns and altered signaling pathways in HER2-positive breast cancer cells after 225Ac-DOTA-trastuzumab intervention and revealed its potential anti-tumor molecular mechanism.Our study provides reliable transcriptomic evidence and research clues for subsequent research and translational development of this targeted alpha therapy agent.