Cheng Ran, Qi Liqiang, Kong Xiangyi, Wang Zhongzhao, Fang Yi, Wang Jing
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Genet. 2020 Sep 29;11:538734. doi: 10.3389/fgene.2020.538734. eCollection 2020.
Breast cancer is the most frequent malignant tumor in women, and the estrogen receptor (ER) plays a vital role in the vast majority of breast cancers. The purpose of the present study was to identify the significant genes regulated by ER in ER-positive breast cancer and to explore their expression pattern changes when tamoxifen or fulvestrant resistance occurs. For this purpose, the gene expression profiles GSE11324, GSE27473, and GSE5840 from the Gene Expression Omnibus database were used, which contain gene expression data from MCF7 cells treated with estrogen, MCF7 cells with silencing of ER, and tamoxifen- and fulvestrant-resistant MCF7 cells treated with estrogen (17β-estradiol), respectively. Differentially expressed genes (DEGs) between the treatment group and negative control were identified and subjected to pathway enrichment and protein-protein interaction (PPI) analyses. There were 230 DEGs in common among the three datasets, including 160 genes positively regulated by ER and 70 genes negatively regulated by ER. DEGs mainly showed enrichment for pathways in cancer, progesterone-mediated oocyte maturation, RNA transport, glycerophospholipid metabolism, oocyte meiosis, platelet activation, and so on. PPI network and modular analysis selected three significant clusters containing 19 genes. A total of 44 genes were involved in Kyoto Encyclopedia of Gene and Genome pathway results or PPI modular analysis, and 16 of them were found to correlate with relapse-free survival in patients with ER/human epidermal growth factor receptor 2-negative breast cancer who had undergone endocrine therapies only. Some of the genes' expression patterns were different among wild-type, tamoxifen-resistant, and fulvestrant-resistant MCF7 cells such as , , , , and , etc., indicating different resistance mechanisms and potential prognostic markers or therapeutic targets for fulvestrant- or tamoxifen-resistant breast cancer.
乳腺癌是女性中最常见的恶性肿瘤，雌激素受体（ER）在绝大多数乳腺癌中起着至关重要的作用。本研究的目的是鉴定雌激素受体阳性乳腺癌中受ER调控的重要基因，并探讨在出现他莫昔芬或氟维司群耐药时它们的表达模式变化。为此，使用了来自基因表达综合数据库的基因表达谱GSE11324、GSE27473和GSE5840，它们分别包含用雌激素处理的MCF7细胞、ER沉默的MCF7细胞以及用雌激素（17β-雌二醇）处理的他莫昔芬和氟维司群耐药的MCF7细胞的基因表达数据。鉴定了治疗组和阴性对照之间的差异表达基因（DEG），并进行了通路富集和蛋白质-蛋白质相互作用（PPI）分析。三个数据集中共有230个DEG，其中包括160个受ER正向调控的基因和70个受ER负向调控的基因。DEG主要在癌症、孕酮介导的卵母细胞成熟、RNA转运、甘油磷脂代谢、卵母细胞减数分裂、血小板活化等通路中显示富集。PPI网络和模块分析选择了包含19个基因的三个重要簇。共有44个基因参与了京都基因与基因组百科全书通路结果或PPI模块分析，其中16个基因被发现与仅接受内分泌治疗的ER/人表皮生长因子受体2阴性乳腺癌患者的无复发生存相关。一些基因的表达模式在野生型、他莫昔芬耐药和氟维司群耐药的MCF7细胞中有所不同，如 、 、 、 、 等，表明存在不同的耐药机制以及氟维司群或他莫昔芬耐药乳腺癌的潜在预后标志物或治疗靶点。
