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Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor

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  • Hailiang Zhang

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Lin Bai

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Xin-Qiang Wu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Xi Tian

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Jinwen Feng

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Xiaohui Wu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Guo-Hai Shi

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Xiaoru Pei

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Jiacheng Lyu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Guojian Yang

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Yang Liu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Wenhao Xu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Aihetaimujiang Anwaier

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Yu Zhu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Da-Long Cao

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Fujiang Xu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

  • Yue Wang

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Hua-Lei Gan

    (Shanghai Medical College, Shanghai Genitourinary Cancer Institute
    Fudan University Shanghai Cancer Center)

  • Meng-Hong Sun

    (Shanghai Medical College, Shanghai Genitourinary Cancer Institute
    Fudan University Shanghai Cancer Center)

  • Jian-Yuan Zhao

    (Shanghai Jiao Tong University School of Medicine
    Zhengzhou University)

  • Yuanyuan Qu

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Dingwei Ye

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University
    Shanghai Medical College, Shanghai Genitourinary Cancer Institute)

  • Chen Ding

    (Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Qingdao Institute, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University)

Abstract

The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic–area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses.

Suggested Citation

  • Hailiang Zhang & Lin Bai & Xin-Qiang Wu & Xi Tian & Jinwen Feng & Xiaohui Wu & Guo-Hai Shi & Xiaoru Pei & Jiacheng Lyu & Guojian Yang & Yang Liu & Wenhao Xu & Aihetaimujiang Anwaier & Yu Zhu & Da-Long, 2023. "Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39981-6
    DOI: 10.1038/s41467-023-39981-6
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