Citation: Qianqian Chen, Ziheng Xu, Jiayi Mu, Xiujuan Hong, Yanqin Huang, Jiekai Yu, Ying Yuan, Ning Zhu, Cheng Guo. Urine metabolic profiling and discovery of potential biomarkers for colorectal cancer using liquid chromatography-high resolution mass spectrometry[J]. Chinese Chemical Letters, ;2026, 37(8): 112327. doi: 10.1016/j.cclet.2025.112327 shu

Urine metabolic profiling and discovery of potential biomarkers for colorectal cancer using liquid chromatography-high resolution mass spectrometry

Qianqian Chen ^a ,
Ziheng Xu ^{a, b} ,
Jiayi Mu ^a ,
Xiujuan Hong ^a ,
Yanqin Huang ^a ,
Jiekai Yu ^a ,
Ying Yuan ^{a, b, c, d} ,
Ning Zhu ^{a, b, *,} ,
Cheng Guo ^{a, c, d, *,}

a.
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
b.
Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
c.
Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou 310009, China
d.
Cancer Center, Zhejiang University, Hangzhou 310058, China

zhuning2017@zju.edu.cn

cheng_guo@zju.edu.cn

Received Date: 14 July 2025
Revised Date: 24 December 2025
Accepted Date: 25 December 2025
Available Online: 25 December 2025

Figures(6)

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and has become a serious threat to human health worldwide. As an important part of systems biology, metabolomics is an effective tool to study the pathogenesis of diseases and search for potential biomarkers. Particularly, liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based untargeted metabolomics plays crucial roles in the discovery of CRC biomarkers. However, previous studies still have some limitations, such as small sample cohorts, lack of standardized procedures and independent validation. In this study, LC-HRMS based non-targeted metabolomics analysis was performed to acquire metabolic profiling of 156 urine samples from healthy controls (HC, n = 43), colorectal adenoma patients (CRA, n = 51) and CRC patients (n = 62) to reveal metabolite disturbance, and then differential metabolites were verified in another sample set including 200 urine samples. Compared with CRA patients and HC, the levels of some lipids and lipid-like molecules, organic acids and derivatives, and organic oxygen compounds were increased, whereas the levels of most amino acids and derivatives, benzenoids, lipids and lipid-like molecules, nucleosides, nucleotides, and analogues, organic acids and derivatives, organoheterocyclic compounds as well as phenylpropanoids and polyketides were significantly decreased in CRC patients. Moreover, a potential biomarkers panel consisting of 4 metabolites was defined and validated for CRC diagnosis, and high area under the curve (0.963 for distinguishing CRC from non-CRC subjects) as well as good specificity and sensitivity were obtained. Although further extensive validation with larger sample sizes in different populations is needed before it can be recommended for clinical use, clinical diagnosis of CRC in the future may benefit from the biomarkers panel developed in this study.
- LC-HRMS,
- Metabolomics,
- Colorectal cancer,
- Biomarker,
- Urine
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