Nature Communications (Jul 2023)
Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor
- 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 Cao,
- Fujiang Xu,
- Yue Wang,
- Hua-Lei Gan,
- Meng-Hong Sun,
- Jian-Yuan Zhao,
- Yuanyuan Qu,
- Dingwei Ye,
- Chen Ding
Affiliations
- Hailiang Zhang
- Department of Urology, 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
- Lin Bai
- Department of Urology, 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
- Department of Urology, 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
- Xi Tian
- Department of Urology, 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
- Jinwen Feng
- Department of Urology, 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
- Department of Urology, 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
- Department of Urology, 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
- Xiaoru Pei
- Department of Urology, 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
- Department of Urology, 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
- Department of Urology, 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
- Department of Urology, 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
- Department of Urology, 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
- Aihetaimujiang Anwaier
- Department of Urology, 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
- Yu Zhu
- Department of Urology, 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
- Da-Long Cao
- Department of Urology, 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
- Fujiang Xu
- Department of Urology, 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
- Department of Urology, 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
- Hua-Lei Gan
- Department of Oncology, Shanghai Medical College, Shanghai Genitourinary Cancer Institute
- Meng-Hong Sun
- Department of Oncology, Shanghai Medical College, Shanghai Genitourinary Cancer Institute
- Jian-Yuan Zhao
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
- Yuanyuan Qu
- Department of Urology, 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
- Dingwei Ye
- Department of Urology, 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
- Chen Ding
- Department of Urology, 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
- DOI
- https://doi.org/10.1038/s41467-023-39981-6
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 21
Abstract
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.
