Tamoxifen (TAM) resistance is finally developed in over 40% of patients with estrogen receptor α‐positive breast cancer (ERα+‐BC), documenting that discovering new molecular subtype is needed to confer perception to the heterogeneity of ERα+‐BC. We obtained representative gene sets subtyping ERα+‐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 ERα+‐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 ERα+‐BC. We further found that minichromosome maintenance complex component 2 (MCM2) functioned as the hub gene subtyping ERα+‐BC using GO, KEGG, and MCODE. MCM2 expression was capable for specifically predicting 1‐year overall survival (OS) of ERα+‐BC and correlated with T stage, AJCC stage, and tamoxifen (TAM) sensitivity of ERα+‐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 ERα+‐BC, providing a novel dimension for discovering a potential target of TAM‐resistant BC.

中文翻译：

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MCM2作为ERα的下游因子参与ERα阳性乳腺癌的亚型分型和他莫昔芬耐药

超过 40% 的雌激素受体 α 阳性乳腺癌 (ERα) 患者最终出现他莫昔芬 (TAM) 耐药性+‐BC），记录了需要发现新的分子亚型来赋予对 ERα 异质性的认识+-公元前。我们获得了代表性基因集 ERα 亚型+‐BC 在 METABRIC、TCGA 和 GEO 数据库的基础上使用基因集变异分析 (GSVA)、非负矩阵分解 (NMF) 和 COX 回归方法。此外，ERα的风险评分+‐基于代表性基因集中的基因，使用最小绝对收缩和选择算子（LASSO）回归建立BC亚型，从而生成ERα的两种亚型+-公元前。我们进一步发现微型染色体维持复合体成分2（MCM2) 作为 ERα 亚型的枢纽基因+‐BC 使用 GO、KEGG 和 MCODE。MCM2表达能够特异性预测 ERα 的 1 年总生存期 (OS)+‐BC 并与 ERα 的 T 分期、AJCC 分期和他莫昔芬 (TAM) 敏感性相关+-公元前。的下调MCM2表达抑制 TAM 耐药细胞的增殖、迁移和侵袭，并促进 G0/G1 期停滞。总而言之，他莫昔芬耐药性意味着MCM2是 ERα 亚型的枢纽基因+‐BC，为发现 TAM 耐药 BC 的潜在靶点提供了一个新的维度。