Genome-wide analysis of the three-way interplay among gene expression, estrogen receptor expression and chemotherapeutic sensitivity in breast cancer

乳腺癌基因表达、雌激素受体表达和化疗敏感性三者相互作用的全基因组分析

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作者:Dong-Xu He, Xiao-Li Wu, Chun-Xiao Lu, Xiao-Ting Gu, Guang-Yuan Zhang, Xin Ma, De-Quan Liu

Abstract

The expression of estrogen receptor α (ER) in breast cancers may be indicative of a favorable prognosis and most of these cancers respond to anti-estrogens or aromatase inhibitors. However, ER-positive (ER+) breast cancers receiving anti-hormone and/or chemotherapy sometimes lose their ER expression, which leads to the evolution of the disease to higher aggressiveness and drug resistance. In the present study, an ER-modified signature (EMS) was developed from the expression profile of a chemoresistant MCF-7 breast cancer cell line that lost ER expression during long-term treatment with a chemotherapeutic agent. The EMS could discriminate the ER-negative (ER-) breast cancer cells from the ER+ ones, which included seven pathways essential for the ER- cell development. Furthermore, the EMS indicated a more malignant subgroup of the ER- cells by discriminating the chemoresistant ER- cells from the chemosensitive ones. In addition, the classified chemoresistant ER- patients demonstrated worse prognosis. In conclusion, we developed a new method to discriminate subgroups of ER- breast cancer cells.

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