MCM2 is involved in subtyping and tamoxifen resistance of ERα-positive breast cancer by acting as the downstream factor of ERα

Tamoxifen (TAM) resistance is finally developed in over 40% of patients with estrogen receptor alpha-positive breast cancer (ER alpha(+)-BC), documenting that discovering new molecular subtype is needed to confer perception to the heterogeneity of ER alpha(+)-BC. We obtained representative gene sets subtyping ER alpha(+)-BC using gene set variation analysis (GSVA), non-negative matrix factorization (NMF), and COX regression methods on the basis of METABRIC, TCGA, and GEO databases. Furthermore, the risk score of ER alpha(+)-BC subtyping was established using least absolute shrinkage and selection operator (LASSO) regression on the basis of genes in the representative gene sets, thereby generating the two subtypes of ER alpha(+)-BC. We further found that minichromosome maintenance complex component 2 (MCM2) functioned as the hub gene subtyping ER alpha(+)-BC using GO, KEGG, and MCODE. MCM2 expression was capable for specifically predicting 1-year overall survival (OS) of ER alpha(+)-BC and correlated with T stage, AJCC stage, and tamoxifen (TAM) sensitivity of ER alpha(+)-BC. The downregulation of MCM2 expression inhibited proliferation, migration, and invasion of TAM-resistant cells and promoted G0/G1 arrest. Altogether, tamoxifen resistance entails that MCM2 is a hub gene subtyping ER alpha(+)-BC, providing a novel dimension for discovering a potential target of TAM-resistant BC.