非靶向代谢组学筛选结直肠癌患者血清标志物

doi:10.16352/j.issn.1001-6325.2025.06.0793

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (6): 793-799.doi: 10.16352/j.issn.1001-6325.2025.06.0793

非靶向代谢组学筛选结直肠癌患者血清标志物

王爱唯¹, 刘佳琦², 刘晓燕¹, 孙海丹¹, 郭正光¹, 何成彦², 孙伟^1*

1.中国医学科学院基础医学研究所北京协和医学院基础学院药理系,北京 100005;
2.吉林大学中日联谊医院检验科,吉林长春 130033

收稿日期:2025-03-12 修回日期:2025-04-03 出版日期:2025-06-05 发布日期:2025-05-26
通讯作者: ^*sunwei@ibms.pumc.edu.cn
基金资助:
北京市自然科学基金(L246002)

Non-targeted metabolomics screening for serum biomarkers in colorectal cancer patients

WANG Aiwei¹, LIU Jiaqi², LIU Xiaoyan¹, SUN Haidan¹, GUO Zhengguang¹, HE Chengyan², SUN Wei^1*

1. Department of Pharmacology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. Department of Clinical Laboratory, China-Japan Union Hospital of Jilin University, Changchun 130033, China

Received:2025-03-12 Revised:2025-04-03 Online:2025-06-05 Published:2025-05-26

摘要/Abstract

摘要： 目的通过非靶向代谢组学筛选结直肠癌(CRC)患者血清中的潜在代谢标志物,并评估其作为诊断和分期生物标志物的价值。方法收集100例健康对照(HC)和100例CRC患者血清,采用超高效液相色谱-质谱联用技术(UPLC-MS)进行非靶向代谢组学分析。数据经归一化后,通过主成分分析(PCA)、正交偏最小二乘判别分析(OPLS-DA)等筛选差异代谢物,并进行通路富集分析。采用单因素及多因素回归评估诊断效能,结合Mfuzz聚类分析CRC分期(Ⅰ~Ⅳ期)相关代谢物。结果共鉴定432个代谢物,59个显著差异。淀粉和蔗糖代谢、甘油磷脂代谢通路显著富集。3种代谢物组合(4,8-dimethylnonanoyl carnitine、9,13-dihydroxy-4-megastigmen-3-one 9-glucoside和C17 sphingosine-1-phosphate)的诊断曲线下面积(AUC)达0.907;分期分析中,L-Carnitine和L-Norleucine组合的AUC为0.776。结论特定血清代谢物组合具有高诊断准确性,且代谢通路异常与CRC进展相关,可作为潜在生物标志物。

关键词: 结直肠癌, 非靶向代谢组学, 超高效液相色谱-质谱联用技术, 血清标志物

Abstract: Objective To identify potential serum metabolic biomarkers in colorectal cancer (CRC) patients using untargeted metabolomics and to evaluate their diagnostic and staging value. Methods Serum samples from 100 healthy controls and 100 CRC patients were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). After data normalization, differential metabolites were screened using multivariate statistical analyses (PCA, OPLS-DA) and subjected to pathway enrichment analysis. Diagnostic performance was assessed via univariate and multivariate regression, while Mfuzz clustering was applied to analyze stage-related metabolites (Ⅰ-Ⅳ). Results A total of 432 metabolites were identified with 59 showing significant alterations. Starch and sucrose metabolism and glycerophospholipid metabolism pathways were significantly enriched. A three-metabolite panel (4,8- dimethylnonanoyl carnitine, 9,13-dihydroxy-4-megastigmen-3-one 9-glucoside and C17 sphingosine-1-phosphate) achieved a diagnostic AUC of 0.907, while L-Carnitine and L-Norleucine showed an AUC of 0.776 in staging analysis. Conclusions Specific serum metabolite panel exhibit high diagnostic accuracy, and dysregulated metabolic pathways are associated with CRC progression, suggesting their potential value as biomarkers.

Key words: colorectal cancer, untargeted metabolomics, UPLC-MS, serum biomarkers

中图分类号:

R735.3

王爱唯, 刘佳琦, 刘晓燕, 孙海丹, 郭正光, 何成彦, 孙伟. 非靶向代谢组学筛选结直肠癌患者血清标志物[J]. 基础医学与临床, 2025, 45(6): 793-799.

WANG Aiwei, LIU Jiaqi, LIU Xiaoyan, SUN Haidan, GUO Zhengguang, HE Chengyan, SUN Wei. Non-targeted metabolomics screening for serum biomarkers in colorectal cancer patients[J]. Basic & Clinical Medicine, 2025, 45(6): 793-799.

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非靶向代谢组学筛选结直肠癌患者血清标志物

Non-targeted metabolomics screening for serum biomarkers in colorectal cancer patients

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