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Li Xumiao, Huang Yiming, Zheng Kuo, Yu Guanyu, Wang Qinqin, Gu Lei, Li Jingquan, Wang Hui, Zhang Wei, Sun Yidi, Li Chen. Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer[J]. Biophysics Reports. doi: 10.52601/bpr.2022.210048
Citation: Li Xumiao, Huang Yiming, Zheng Kuo, Yu Guanyu, Wang Qinqin, Gu Lei, Li Jingquan, Wang Hui, Zhang Wei, Sun Yidi, Li Chen. Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer[J]. Biophysics Reports. doi: 10.52601/bpr.2022.210048

Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer

doi: 10.52601/bpr.2022.210048
Funds:  This work was supported by the National Natural Science Foundation of China (NSFC) (82030099, 82072750, 30700397), the Shanghai Municipal Science and Technology Commission "Science and Technology Innovation Action Plan" technical standard project (21DZ2201700), the Natural Science Fund of Shanghai (20ZR1457200), Shanghai Sailing Program (21YF1459300), and the innovative research team of high-level local universities in Shanghai.
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  • Mass spectrometry (MS)-based proteomics and phosphoproteomics are powerful methods to study the biological mechanisms, diagnostic biomarkers, prognostic analysis, and drug therapy of tumors. Data-independent acquisition (DIA) mode is considered to perform better than data-dependent acquisition (DDA) mode in terms of quantitative reproducibility, specificity, accuracy, and identification of low-abundance proteins. Mini patient derived xenograft (MiniPDX) model is an effective model to assess the response to antineoplastic drugs in vivo and is helpful for the precise treatment of cancer patients. Kinases are favorable spots for tumor-targeted drugs, and their functional completion relies on signaling pathways through phosphorylating downstream substrates. Kinase-phosphorylation networks or edge interactions are considered more credible and permanent for characterizing complex diseases. Here, we provide a workflow for personalized drug response assessment in primary and metastatic colorectal cancer (CRC) tumors using DIA proteomic data, DIA phosphoproteomic data, and MiniPDX models. Three kinase inhibitors, afatinib, gefitinib, and regorafenib, are tested pharmacologically. The process mainly includes the following steps: clinical tissue collection, sample preparation, hybrid spectral libraries establishment, MS data acquisition, kinase-substrate network construction, in vivo drug test, and elastic regression modeling. Our protocol gives a more direct data basis for individual drug responses, and will improve the selection of treatment strategies for patients without the druggable mutation.
  • Xumiao Li, Yiming Huang, Kuo Zheng, Guanyu Yu, Qinqin Wang, Lei Gu, Jingquan Li, Hui Wang, Wei Zhang, Yidi Sun and Chen Li declare that they have no conflict of interest.
    All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed.
    # Xumiao Li, Yiming Huang, Kuo Zheng and Guanyu Yu contributed equally to this work.
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