Cancer biomarkers discovered using pan-cancer plasma proteomic profiling

Lin Bai^#¹, Jiacheng Lyu^#¹, Jinwen Feng^#¹, Xiaoqiang Qiao^#^{2

3}, Yuanyuan Qu^#^{1

4}, Guojian Yang^#¹, Yuanxue Zhu^#², Lingxiao Liao^#⁵, Hui Gao⁶, Aimin Zang², Zeya Xu¹, Tao Ji¹, Peng Ran¹, Wencong Ding⁵, Hailiang Zhang^{1

4}, Lingli Zhu¹, Yan Wang⁷, Liang Wang⁸, Xiaofang Wang², Yumiao Li², Jinghua Li⁹, Xiaoping Yin¹⁰, Guofa Zhao², Dan Liu^{11

12}, Xiangpeng Gao^{11

12}, Sha Tian¹, Subei Tan¹, Yan Pu¹, Lingling Li¹, Zizheng Song², Jin Song², Wenjia Guo¹³, Yongshi Liao¹⁴, Dingwei Ye^{15

16}, Wenjun Yang¹⁷, Youchao Jia¹⁸, Chen Ding^{19

20}

Affiliations

¹ Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer Center, Center for Cell and Gene Therapy, Fudan University, Shanghai, China.
² Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei, China.
³ College of Pharmaceutical Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry of Education, Hebei University, Baoding, China.
⁴ Department of Oncology, Shanghai Medical College, Shanghai Genitourinary Cancer Institute, Shanghai, China.
⁵ Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China.
⁶ Hebei Normal University of Science and Technology, Qinhuangdao, China.
⁷ Clinical Lab, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
⁸ Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
⁹ Department of Hepatological Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
¹⁰ CT/MRI room, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
¹¹ College of Clinical Medicine, Hebei University, Baoding, China.
¹² Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, China.
¹³ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, China.
¹⁴ Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China. liaoys66@163.com.
¹⁵ Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer Center, Center for Cell and Gene Therapy, Fudan University, Shanghai, China. dwyeli@163.com.
¹⁶ Department of Oncology, Shanghai Medical College, Shanghai Genitourinary Cancer Institute, Shanghai, China. dwyeli@163.com.
¹⁷ Department of Pediatric Orthopedics, Spine Center, Xin Hua Hospital Affiliated to, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wjyang@sibcb.ac.cn.
¹⁸ Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei, China. youchaojia1@163.com.
¹⁹ Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer Center, Center for Cell and Gene Therapy, Fudan University, Shanghai, China. chend@fudan.edu.cn.
²⁰ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, China. chend@fudan.edu.cn.

^# Contributed equally.

PMID: 40603747
DOI: 10.1038/s41551-025-01448-y

Cancer biomarkers discovered using pan-cancer plasma proteomic profiling

Lin Bai et al. Nat Biomed Eng. 2025.

. 2025 Jul 2.

doi: 10.1038/s41551-025-01448-y. Online ahead of print.

Authors

Affiliations

¹ Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer Center, Center for Cell and Gene Therapy, Fudan University, Shanghai, China.
² Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei, China.
³ College of Pharmaceutical Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry of Education, Hebei University, Baoding, China.
⁴ Department of Oncology, Shanghai Medical College, Shanghai Genitourinary Cancer Institute, Shanghai, China.
⁵ Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China.
⁶ Hebei Normal University of Science and Technology, Qinhuangdao, China.
⁷ Clinical Lab, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
⁸ Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
⁹ Department of Hepatological Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
¹⁰ CT/MRI room, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
¹¹ College of Clinical Medicine, Hebei University, Baoding, China.
¹² Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, China.
¹³ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, China.
¹⁴ Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China. liaoys66@163.com.
¹⁵ Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer Center, Center for Cell and Gene Therapy, Fudan University, Shanghai, China. dwyeli@163.com.
¹⁶ Department of Oncology, Shanghai Medical College, Shanghai Genitourinary Cancer Institute, Shanghai, China. dwyeli@163.com.
¹⁷ Department of Pediatric Orthopedics, Spine Center, Xin Hua Hospital Affiliated to, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wjyang@sibcb.ac.cn.
¹⁸ Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei, China. youchaojia1@163.com.
¹⁹ Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer Center, Center for Cell and Gene Therapy, Fudan University, Shanghai, China. chend@fudan.edu.cn.
²⁰ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, China. chend@fudan.edu.cn.

^# Contributed equally.

PMID: 40603747
DOI: 10.1038/s41551-025-01448-y

Abstract

Mass-spectrometry-based proteomic data of tumour patient plasma samples present opportunities for improving cancer detection. Here we generate plasma proteomic profiles from 2,251 pan-cancer patient samples and investigate potential diagnostic biomarkers. Proteomic subtyping with different dominant tumour types links proteomic features and clinical indicators such as tumour stage. The highly immune-activated subtype, consisting of renal and bladder cancers, shows elevated glucose-insulin metabolism and reduced lipid metabolism. Comparison of the plasma proteome before and after surgery indicates that proteome patterns could be used to monitor post-surgery therapeutic effects. We also develop a binary classified model that distinguishes between tumour types and healthy controls, as well as a multicancer model for pan-cancer classification of proteins that could be useful biomarkers, and validate their performance in an independent cohort. In addition, we find that the plasma proteome, along with clinical indicators, whole blood cells and so on, can distinguish the pathological subtypes of specific tumour types. This study portrays a pan-cancer plasma proteomic landscape, providing information on plasma biomarkers that could help in discovering diagnostic opportunities.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70, 7–30 (2020). - PubMed - DOI
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Cancer biomarkers discovered using pan-cancer plasma proteomic profiling

Affiliations

Cancer biomarkers discovered using pan-cancer plasma proteomic profiling

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources