Ung Matthew H, Wang George L, Varn Frederick S, Cheng Chao
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, 03755 USA.
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, 03755 USA.
Oncotarget. 2016 Dec 20;7(51):84142-84154. doi: 10.18632/oncotarget.11776.
The PI3K-Akt-mTOR signaling pathway has been identified as a key driver of carcinogenesis in several cancer types. As such, a major area of focus in cancer biology is the development of genomic biomarkers that can measure the activity level of the PI3K-Akt-mTOR pathway. In this study, we systematically estimate PI3K-Akt-mTOR pathway activity in breast primary tumor samples using transcriptomic profiles derived from drug treatment in MCF7 cell lines. We demonstrate that gene expression profiles derived from chemically-induced protein inhibition allows us to measure PI3K-Akt-mTOR pathway activity in patient tumor samples. With this approach, we predict prognosis and response to chemotherapy in cancer patients, and screen for potential pharmacological modulators of PI3K-Akt-mTOR pathway inhibitors.
PI3K-Akt-mTOR信号通路已被确定为多种癌症类型中致癌作用的关键驱动因素。因此，癌症生物学的一个主要研究重点是开发能够测量PI3K-Akt-mTOR通路活性水平的基因组生物标志物。在本研究中，我们使用源自MCF7细胞系药物治疗的转录组谱，系统地估计乳腺原发性肿瘤样本中的PI3K-Akt-mTOR通路活性。我们证明，化学诱导的蛋白质抑制产生的基因表达谱使我们能够测量患者肿瘤样本中的PI3K-Akt-mTOR通路活性。通过这种方法，我们预测癌症患者的预后和对化疗的反应，并筛选PI3K-Akt-mTOR通路抑制剂的潜在药理调节剂。
