Analyzing the differentially expressed genes and pathway cross‐talk in aggressive breast cancer

Abstract Aim The aim of this study was to explore the genes and pathways involved in the aggressive breast cancer cells. Methods The gene expression profiles of GSE 40057, including four aggressive breast cell lines and six less aggressive cell lines, were downloaded from the G ene E xpression O mnibus ( GEO ) database. The gene differential expression analysis was carried out with limma software with the method of B ayes for multiple tests. The gene ontology ( GO ) term enrichment and pathway cross‐talk analysis were performed with the online tool of DAVID and C ytoscape software. Results A total of 401 differentially expressed genes ( DEG ), such as pentraxin 3 ( PTX 3), snail family zinc finger 2 ( SNAI 2), interleukin‐8/6 ( IL ‐8/6), osteonectin ( SPARC ), matrix metallopeptidase‐1 ( MMP ‐1) and R as‐related protein R ab‐25 ( R ab 25), were identified between aggressive and less aggressive cell lines. They were mainly enriched in the GO terms of response to wounding, negative regulation of cell proliferation and calcium binding. Pathways in cancer dysfunctionally interacted with glyoxylate and dicarboxylate metabolism ( P < 0.0001), basal transcription factors ( P < 0.0001), tyrosine metabolism ( P < 0.0001), calcium signaling pathway ( P = 0.0021), FcγR‐mediated phagocytosis ( P = 0.0022), metabolism of xenobiotics by cytochrome P 450 ( P = 0.0097) and phagosome ( P = 0.0102). Conclusion The screened aggressive cancer‐associated DEG ( PTX 3, SNAI 2, IL ‐8/6, SPARC , MMP ‐1 and R ab25) and significant pathways (calcium signaling pathway, tyrosine metabolism, alanine, aspartate and glutamate metabolism) give us new insights into the mechanism of aggressive breast cancer cells, and these DEG may become promising target genes in the treatment of metastatic breast cancer.