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Hunt for the tipping point during endocrine resistance process in breast cancer by dynamic network biomarkers

机译:通过动态网络生物标记物寻找乳腺癌内分泌抵抗过程中的临界点

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机译:Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant.

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  • 来源
    《分子细胞生物学报:英文版》 |2019年第8期|P.649-664|共16页
  • 作者单位

    School of Mathematics South China University of Science and Technology Guangzhou 510640 China;

    School of Life Sciences and Technology Tongji University Shanghai 200092 China;

    National Research Center for Translational Medicine (Shanghai) Rui Jin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China;

    Graduate School of Medical Life Science Yokohama City University Yokohama 230-0045 Japan;

    Laboratory for Integrated Cellular Systems RIKEN Center for Integrative Medical Sciences (IMS) Yokohama 230-0045 Japan;

    Key Laboratory of Systems Biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai 200031 China;

    Department of Medical Genome Sciences Graduate School of Frontier Sciences The University of Tokyo Chiba 277-8562 Japan;

    Institute of Industrial Science The University of Tokyo Tokyo 153-8505 Japan;

    Laboratory of Cell Systems Osaka University Osaka 565-0871 Japan;

    Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Kunming 650223 China;

    School of Life Science and Technology ShanghaiTech University Shanghai 200031 China;

    Shanghai Research Center for Brain Science and Brain-Inspired Intelligence Shanghai 201210 China;

  • 收录信息 中国科学引文数据库(CSCD);
  • 原文格式 PDF
  • 正文语种 chi
  • 中图分类 生物科学;
  • 关键词

    drug resistance; breast cancer; tipping point; dynamic network biomarker (DNB); molecular network; mRNA-seq;

    机译:耐药性;乳腺癌;引爆点;动态网络生物标记(DNB);分子网络mRNA序列;
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