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Proteomics provides individualized options of precision medicine for patients with gastric cancer

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Abstract

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2017YFC1308900, 2017YFC0908404, 2018YFA0507503, 2017YFA0505103), Beijing Municipal Government Key Research and Development Program (Z181100001918020, Z161100002616036), the National Natural Science Foundation of China (31870828, 81972790, 81672319), the Guangdong Provincial Key R&D Programmes (2019B020229002), the Science and Technology Program of Guangzhou (201902020009), the National Key Basic Research Program of China (2014CBA02002), and the National Key Technology Support Program (2015BAI13B07). This work is dedicated to the memory of Dr. Bei Zhen. We thank the following people for their contributions: all the patients who participated in this study; the clinicians and staff of the institutions who assisted with the studies; and Drs. Jing Gao, Sai Ge, Yanyan Li, Xiaoyi Chong (Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute) for assistance with data management and logistic support; and Dongmei Lin, Zhongwu Li, Bin Dong (Department of Pathology, Peking University Cancer Hospital and Institute) for assistance with sample evaluation.

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Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China

    Wenwen Huang, Cheng Zhang, Zhihao Lu & Lin Shen

  2. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China

    Dongdong Zhan, Nairen Zheng, Xin Wei, Mingwei Liu, Xuefei Zhao, Xiaotian Ni, Xia Xia, Jinwen Shi, Weimin Zhu, Yi Wang & Jun Qin

  3. Department of Pathology, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China

    Yazhuo Li & Hongwei Wang

  4. State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, 710032, China

    Bin Bai, Juan Wang, Shiqi Wang, Gang Ji, Jipeng Li, Yongzhan Nie & Qingchuan Zhao

  5. Department of General Surgery & Institute of General Surgery, Chinese PLA General Hospital First Medical Center, Beijing, 100853, China

    Kecheng Zhang, Wenquan Liang, Xiaosong Wu, Jianxin Cui & Lin Chen

  6. Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China

    Jiafu Ji

  7. Department of tumor biobank, Shanxi Cancer Hospital, Taiyuan, 030013, China

    Yongsheng Meng & Feilin Cao

  8. Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China

    Dongdong Zhan & Tieliu Shi

  9. State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai, 200433, China

    Jun Qin

  10. Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China

    Xin Wei

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Correspondence to Lin Chen, Qingchuan Zhao, Hongwei Wang, Lin Shen or Jun Qin.

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Huang, W., Zhan, D., Li, Y. et al. Proteomics provides individualized options of precision medicine for patients with gastric cancer. Sci. China Life Sci. 64, 1199–1211 (2021). https://doi.org/10.1007/s11427-021-1966-4

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