Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis

Abstract

Breast cancer (BC) is one of the leading causes of death among women worldwide. The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein–protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation. Eight hub genes were identified from the PPI network, including GSK3B, RAC1, PXN, ERBB2, HSP90AA1, FGF2, PIK3R1 and RAC2. Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin. In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.