Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis

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, Shuangmei Zou, Jiajia Gao, Yan Zhao, Peng Nan, Xiufeng Xie, Fang Liu, Lanping Zhou, Wei Sun () and Xiaohang Zhao ()
Additional contact information
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

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30391-8

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