Integrative Bioinformatics Analysis Reveals CHEK1 and UBE2C as Luminal A Breast Cancer Subtype Biomarkers

In light of the limited number of targetable oncogenic drivers in breast cancer (BRCA), it is important to identify effective and druggable gene targets for the treatment of this devastating disease. Herein, the GSE102484 dataset containing expression profiling data from 683 BRCA patients was re-analyzed using weighted gene co-expression network analysis (WGCNA). The yellow module with the highest correlation to BRCA progression was screened out, followed by functional enrichment analysis and establishment of a protein–protein interaction (PPI) network. After further validation through survival analysis and expression evaluation, CHEK1 and UBE2C were finally identified as hub genes related to the progression of BRCA, especially the luminal A breast cancer subtype. Notably, both hub genes were found to be dysregulated in multiple types of immune cells and closely correlated with tumor infiltration, as revealed by Tumor Immune Estimation Resource (TIMER) along with other bioinformatic tools. Construction of transcription factors (TF)-hub gene network further confirmed the existence of 11 TFs which could regulate both hub genes simultaneously. Our present study may facilitate the invention of targeted therapeutic drugs and provide novel insights into the understanding of the mechanism beneath the progression of BRCA.