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用于研究多胺在结直肠癌早期诊断和治疗中的价值的定量代谢组学

Quantitative metabolomics for investigating the value of polyamines in the early diagnosis and therapy of colorectal cancer.

作者信息

Liu Ran, Lin Xiaohui, Li Zuojing, Li Qing, Bi Kaishun

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.

School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, 110016, China.

出版信息

Oncotarget. 2017 Dec 4;9(4):4583-4592. doi: 10.18632/oncotarget.22885. eCollection 2018 Jan 12.

Abstract

As an important biomarker for cancer, polyamine levels in body fluid could be employed for monitoring the colorectal cancer (CRC), however the role of polyamines in the development and therapeutics phases of CRC remains uncertain. In this paper, the relationship between polyamines and CRC development and therapeutics had been investigated by the study of changes in plasma polyamine levels during the precancerous, developmental and treatment phases of CRC. After inducing CRC in Wistar rats by intraperitoneal injection of 1, 2-dimethylhydrazine, the animals were given a traditional Chinese medicine, Aidi injections. Firstly, the polyamine levels in the plasma of CRC, healthy and medicated rats were measured by UHPLC-MS/MS assay. In addition, Lasso regression analysis was used for screening and confirming the key markers, which can be employed for distinguishing the healthy and CRC rats as well as the CRC and medication rats. The results obtained showed that polyamine metabolism had been disrupted by CRC but returned to normal levels following Aidi injections and, in particular, putrescine and agmatine were closely correlated with CRC. Our results demonstrate the potential value of plasma polyamine metabolic profiling during the early diagnosis and medical treatment of CRC. Also, the integrated method of polyamine metabolite target analysis and lasso regression analysis can be applied in metabolomics for seeking the differential metabolites.

摘要

作为癌症的一种重要生物标志物,体液中的多胺水平可用于监测结直肠癌(CRC),然而多胺在CRC发生发展及治疗阶段中的作用仍不明确。本文通过研究CRC癌前、发展及治疗阶段血浆多胺水平的变化,探讨了多胺与CRC发生发展及治疗之间的关系。通过腹腔注射1,2 - 二甲基肼诱导Wistar大鼠患CRC后,给这些动物注射中药艾迪注射液。首先,采用超高效液相色谱 - 串联质谱法(UHPLC - MS/MS)测定CRC大鼠、健康大鼠及用药大鼠血浆中的多胺水平。此外,采用套索回归分析筛选并确认关键标志物,这些标志物可用于区分健康大鼠与CRC大鼠以及CRC大鼠与用药大鼠。所得结果表明,CRC会破坏多胺代谢,但艾迪注射液注射后多胺代谢恢复至正常水平,尤其是腐胺和胍丁胺与CRC密切相关。我们的研究结果证明了血浆多胺代谢谱在CRC早期诊断和治疗中的潜在价值。此外,多胺代谢物靶向分析与套索回归分析相结合的方法可应用于代谢组学以寻找差异代谢物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d416/5796997/6268185a78a9/oncotarget-09-4583-g001.jpg

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