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Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis

Author

Listed:
  • Yulin Sun

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhengguang Guo

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiaoyan Liu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lijun Yang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zongpan Jing

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Meng Cai

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhaoxu Zheng

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Chen Shao

    (Beijing Institute of Lifeomics)

  • Yefan Zhang

    (Chinese Academy of Medical Science and Peking Union Medical College)

  • Haidan Sun

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Li Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Minjie Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jun Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lusong Tian

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yue Han

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Shuangmei Zou

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jiajia Gao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yan Zhao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Peng Nan

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiufeng Xie

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Fang Liu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lanping Zhou

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wei Sun

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiaohang Zhao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Currently, imaging, fecal immunochemical tests (FITs) and serum carcinoembryonic antigen (CEA) tests are not adequate for the early detection and evaluation of metastasis and recurrence in colorectal cancer (CRC). To comprehensively identify and validate more accurate noninvasive biomarkers in urine, we implement a staged discovery-verification-validation pipeline in 657 urine and 993 tissue samples from healthy controls and CRC patients with a distinct metastatic risk. The generated diagnostic signature combined with the FIT test reveals a significantly increased sensitivity (+21.2% in the training set, +43.7% in the validation set) compared to FIT alone. Moreover, the generated metastatic signature for risk stratification correctly predicts over 50% of CEA-negative metastatic patients. The tissue validation shows that elevated urinary protein biomarkers reflect their alterations in tissue. Here, we show promising urinary protein signatures and provide potential interventional targets to reliably detect CRC, although further multi-center external validation is needed to generalize the findings.

Suggested Citation

  • Yulin Sun & Zhengguang Guo & Xiaoyan Liu & Lijun Yang & Zongpan Jing & Meng Cai & Zhaoxu Zheng & Chen Shao & Yefan Zhang & Haidan Sun & Li Wang & Minjie Wang & Jun Li & Lusong Tian & Yue Han & Shuangm, 2022. "Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30391-8
    DOI: 10.1038/s41467-022-30391-8
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    References listed on IDEAS

    as
    1. Ruedi Aebersold & Matthias Mann, 2016. "Mass-spectrometric exploration of proteome structure and function," Nature, Nature, vol. 537(7620), pages 347-355, September.
    2. Yunee Kim & Jouhyun Jeon & Salvador Mejia & Cindy Q Yao & Vladimir Ignatchenko & Julius O Nyalwidhe & Anthony O Gramolini & Raymond S Lance & Dean A Troyer & Richard R Drake & Paul C Boutros & O. John, 2016. "Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
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    1. Xiaohua Xing & Linsheng Cai & Jiahe Ouyang & Fei Wang & Zongman Li & Mingxin Liu & Yingchao Wang & Yang Zhou & En Hu & Changli Huang & Liming Wu & Jingfeng Liu & Xiaolong Liu, 2023. "Proteomics-driven noninvasive screening of circulating serum protein panels for the early diagnosis of hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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