乳腺癌中如何靠谱地选定治疗的靶点:多组学综合分析
  • 文章应用基因组学和蛋白质组学的工具,比对和验证了24例乳腺癌移植瘤模型可能的抗癌靶点;
  • 多数情况下,基因组学和蛋白质组学预测结果类似: 比如受体酪氨酸激酶(RTK)的活性;
  • 但是也有一些不一致: 比如AKT高表达和 ARAF, BRAF, HSP90AB1 磷酸化位点;
  • 所以需要同时结合基因组学和蛋白质组学的结果,综合分析,才能选定靠谱的靶点;
  • 在移植瘤模型中应用综合分析,对HER2扩增以及PI3K信号通路活化的肿瘤进行治疗,获得了成功。
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Proteogenomic integration reveals therapeutic targets in breast cancer xenografts

应用蛋白质组学、基因组学、异种移植瘤模型研究乳腺癌治疗靶点

10.1038/ncomms14864

2017-03-28, Article

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Abstract:收起
Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities.

First Authors:
Kuan-Lin Huang,Shunqiang Li,Philipp Mertins

Correspondence Authors:
Matthew J Ellis,Li Ding

All Authors:
Kuan-Lin Huang,Shunqiang Li,Philipp Mertins,Song Cao,Harsha P Gunawardena,Kelly V Ruggles,D R Mani,Karl R Clauser,Maki Tanioka,Jerry Usary,Shyam M Kavuri,Ling Xie,Christopher Yoon,Jana W Qiao,John Wrobel,Matthew A Wyczalkowski,Petra Erdmann-Gilmore,Jacqueline E Snider,Jeremy Hoog,Purba Singh,Beifung Niu,Zhanfang Guo,Sam Qiancheng Sun,Souzan Sanati,Emily Kawaler,Xuya Wang,Adam Scott,Kai Ye,Michael D McLellan,Michael C Wendl,Anna Malovannaya,Jason M Held,Michael A Gillette,David Fenyö,Christopher R Kinsinger,Mehdi Mesri,Henry Rodriguez,Sherri R Davies,Charles M Perou,Cynthia Ma,R Reid Townsend,Xian Chen,Steven A Carr,Matthew J Ellis,Li Ding

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