ARHGEF6 downregulation as a key mediator of tumor cell apoptosis in breast cancer

The present study aimed to identify novel clinical biomarkers for breast cancer (BRCA) through bioinformatics analyses and cellular experiments, due to the ongoing need for improved diagnosis and prognosis in BRCA. The GSE21422 and The Cancer Genome Atlas-BRCA (TCGA-BRCA) datasets were utilized to identify differentially expressed genes (DEGs) in BRCA. Common DEGs were subjected to comprehensive analyses, including risk score modeling, expression profiling, receiver operating characteristic curve evaluation, survival analysis and the development of a prognostic nomogram, to pinpoint clinically significant genes. Cellular assays were subsequently performed to investigate the functional roles of these key genes in BRCA. Through bioinformatics analyses, 5 genes with diagnostic value were identified: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1), Rac/Cdc42 guanine nucleotide exchange factor 6 (ARHGEF6), enhancer of zeste 2 polycomb repressive complex 2 subunit, integrin α1 (ITGA1) and PIK3R1, as well as 3 genes with prognostic value: ALDH1A1, ARHGEF6 and ITGA1. Among them, ARHGEF6 was recognized as the key gene in BRCA. Overexpression of ARHGEF6 was shown to suppress cell proliferation, invasion and migration, while promoting apoptosis in BRCA. In conclusion, by bioinformatics analysis, new diagnostic and prognostic biomarkers for patients with BRCA have been identified and the key gene, ARHGEF6, is a suppressor gene in BRCA progression. These findings provide new directions for BRCA clinical application.