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通过血浆代谢组学发现和验证用于检测结直肠癌的新型生物标志物

Discovery and Validation of Novel Biomarkers for Colorectal Neoplasia Detection via Plasma Metabolomics.

作者信息

Huang Jianv, Wang Le, Zhang Xiang, Liu Xinyi, Miao Junyan, Shen Yuefan, Fu Chengqu, Ge Xianxiu, Wang Xue, Hu Jiancong, Li Guanman, Sun Yang, Miao Yinglei, Dai Juncheng, Du Lingbin, Ma Hongxia, Jin Guangfu, Li Ni, Miao Lin, Hu Zhibin, He Xiaosheng, Yu Jun, Shen Hongbing, Hang Dong

机构信息

Department of Epidemiology Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine School of Public Health Nanjing Medical University Nanjing China.

Zhejiang Provincial Office for Cancer Prevention and Control, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences Hangzhou China.

出版信息

MedComm (2020). 2025 Jun 6;6(6):e70201. doi: 10.1002/mco2.70201. eCollection 2025 Jun.

DOI:10.1002/mco2.70201
PMID:40487747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12141919/
Abstract

Metabolic disturbance plays a critical role in the initiation of colorectal cancer (CRC), yet the identification of metabolites that are useful for early detection of CRC and its precursor lesions remains elusive. We conducted an untargeted plasma metabolomic profiling by liquid chromatography-mass spectrometry in a two-stage case-control study, including 219 CRC cases, 164 colorectal adenoma (CRA) cases, and 219 normal controls (NC) as a training set, and 91 CRC, 115 CRA, and 109 NC as a validation set. Among 891 named metabolites, 239 were significantly altered in CRC versus NC, 26 in CRA versus NC, and 88 in CRC versus CRA within the training set. The results were stable when adjusting for potential confounders. A panel of 10 metabolites, including six lipid species, one benzenoid, one organoheterocyclic compound, one organic acid derivative, and one organic oxygen compound, showed optimal performance in discriminating CRC from NC (AUC = 0.81) in the validation. Moreover, a panel of seven metabolites exhibited optimal performance in discriminating CRA from NC, with an AUC of 0.89. Our findings provide novel evidence supporting specific plasma metabolites, particularly those implicated in lipid metabolism, as promising biomarkers for the early detection of CRC.

摘要

代谢紊乱在结直肠癌(CRC)的发生中起关键作用,然而,对于有助于早期检测CRC及其前驱病变的代谢物的识别仍然难以捉摸。我们在一项两阶段病例对照研究中,通过液相色谱 - 质谱法进行了非靶向血浆代谢组学分析,该研究包括219例CRC病例、164例结直肠腺瘤(CRA)病例和219例正常对照(NC)作为训练集,以及91例CRC、115例CRA和109例NC作为验证集。在891种命名代谢物中,在训练集中,与NC相比,239种在CRC中显著改变,与NC相比,26种在CRA中显著改变,与CRA相比,88种在CRC中显著改变。在调整潜在混杂因素后,结果稳定。一组10种代谢物,包括六种脂质、一种苯类、一种有机杂环化合物、一种有机酸衍生物和一种有机氧化合物,在验证中表现出区分CRC与NC的最佳性能(AUC = 0.81)。此外,一组七种代谢物在区分CRA与NC方面表现出最佳性能,AUC为0.89。我们的研究结果提供了新的证据,支持特定的血浆代谢物,特别是那些与脂质代谢有关的代谢物,作为CRC早期检测的有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/c753e530020b/MCO2-6-e70201-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/ac48dc5c1998/MCO2-6-e70201-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/46b51e0d4da4/MCO2-6-e70201-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/479af810c660/MCO2-6-e70201-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/0406e4e3c57b/MCO2-6-e70201-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/e27bdc07162a/MCO2-6-e70201-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/c753e530020b/MCO2-6-e70201-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/ac48dc5c1998/MCO2-6-e70201-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/46b51e0d4da4/MCO2-6-e70201-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/479af810c660/MCO2-6-e70201-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/0406e4e3c57b/MCO2-6-e70201-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/e27bdc07162a/MCO2-6-e70201-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d2/12141919/c753e530020b/MCO2-6-e70201-g006.jpg

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本文引用的文献

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Tumor biomarkers for diagnosis, prognosis and targeted therapy.肿瘤标志物用于诊断、预后和靶向治疗。
Signal Transduct Target Ther. 2024 May 20;9(1):132. doi: 10.1038/s41392-024-01823-2.
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.
4
Disease Burden of Total and Early-Onset Colorectal Cancer in China from 1990 to 2019 and Predictions of Cancer Incidence and Mortality.1990年至2019年中国总体及早发性结直肠癌的疾病负担以及癌症发病率和死亡率预测
Clin Epidemiol. 2023 Feb 1;15:151-163. doi: 10.2147/CLEP.S391058. eCollection 2023.
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Discovery of plasma biomarkers for colorectal cancer diagnosis via untargeted and targeted quantitative metabolomics.通过非靶向和靶向定量代谢组学发现用于结直肠癌诊断的血浆生物标志物
Clin Transl Med. 2022 Apr;12(4):e805. doi: 10.1002/ctm2.805.
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Serum untargeted lipidomics by UHPLC-ESI-HRMS aids the biomarker discovery of colorectal adenoma.UHPLC-ESI-HRMS 进行非靶向脂质组学分析有助于结直肠腺瘤的生物标志物发现。
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