Bioinformatics analysis of key genes and potential mechanism in cadmium-induced breast cancer progression

Cadmium (Cd) may be associated with breast cancer progression, but the detailed molecular mechanism has not been fully elucidated. In this study, one public dataset (GSE136595) was used to identify differentially expressed genes (DEGs) in Cd-treated MCF-7 breast cancer cells. We determined a total of 2077 DEGs, and Ingenuity Pathway Analysis (IPA) software showed that 246 of them were related to tumor progression. Pathway analysis of these DEGs indicated that the HIF1 alpha signaling and the epithelial-mesenchymal transition (EMT) pathway regulated by growth factors might be activated. Moreover, twist family bHLH transcription factor 1 (TWIST1), lysine demethylase 3A (KDM3A), Kruppel-like factor 4 (KLF4), nuclear protein 1 (NUPR1), neurogenin 3 (NEUROG3), and HNF1 homeobox B (HNF1B) might be the key transcription factors. And the result of protein-protein interaction (PPI) analysis showed that the hub genes in these 246 DEGs were tumor protein p53 (TP53), polo-like kinase 1 (PLK1), sirtuin 1 (SIRT1), protein tyrosine phosphatase non-receptor type 11 (PTPN11), caspase 8 (CASP8), cyclin-dependent kinase 6 (CDK6), calmodulin 3 (CALM3), KRAS proto-oncogene (KRAS), extra spindle pole bodies like 1 (ESPL1), and marker of proliferation Ki-67 (MKI67). Further analysis indicated that TWIST1, NUPR1, KRAS, and PTPN11 were related to the prognostic of breast cancer based on the Cancer Genome Atlas (TCGA) and they were validated to be upregulated in the Cd-treated MCF-7 cells. Our results suggested that the HIF1 alpha signaling and the EMT pathway regulated by growth factors might be participant in the Cd-induced breast cancer progression and TWIST1, NUPR1, KRAS, and PTPN11 might be potential key genes.

Automated summary

This study identified differentially expressed genes in Cd-treated MCF-7 breast cancer cells using a public dataset, revealing that the HIF1 alpha signaling pathway and the epithelial-mesenchymal transition pathway may be involved in Cd-induced breast cancer progression. TWIST1, NUPR1, KRAS, and PTPN11 were identified as potential key genes related to breast cancer prognosis.