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基于 LC-MS/MS 定量检测 NSCLC 患者的血浆氨基酸、嘌呤、三羧酸循环代谢物和脂质水平的评估。

Assessment of plasma amino acids, purines, tricarboxylic acid cycle metabolites, and lipids levels in NSCLC patients based on LC-MS/MS quantification.

机构信息

School of Pharmacy, National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.

School of Food and Drug, Shenzhen Polytechnic, 7098 Lau sin Avenue, Shenzhen 518000, China.

出版信息

J Pharm Biomed Anal. 2022 Nov 30;221:114990. doi: 10.1016/j.jpba.2022.114990. Epub 2022 Aug 8.

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of malignant tumor of the lung with poor prognosis. Currently, there is still no effective strategy for diagnosing lung cancer from the perspective of multiple biomarkers containing both polar and nonpolar molecules. In order to explore the pathological changes of NSCLC at the endogenous molecule levels, and further establish the strategy for identifying and monitoring drug efficacy of NSCLC, targeted metabolomics and lipidomics studies were established with NSCLC patients. Polar metabolites including 21 amino acids, 7 purines, 6 tricarboxylic acid (TCA) cycle metabolites, and nonpolar lipids like phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), and ceramide (Cer), diacylglycerol (DG), triacylglycerol (TG), were quantitatively determined based on LC-MS/MS, taking into account their metabolism were significantly concerned with the occurrence of lung cancer in previous study. As a result, 14 polar metabolites and 16 lipids were prominently altered in the plasma of NSCLC patients, among which, after multivariate statistical analysis, LPC 18:0 (sn-2), L-Phenylalanine (Phe), oxaloacetic acid (OAA) and xanthine (XA) were screened out as potential small molecules and lipid biomarkers for NSCLC. Furthermore, a new strategy for formulating equation of NSCLC identification was proposed and clinical utility was successfully evaluated through Kangai injection treatment to NSCLC patients. Taking together, this study investigated the pathological changes of NSCLC from the perspective of endogenous polar and nonpolar molecules, and shed a light on identification of NSCLC.

摘要

非小细胞肺癌(NSCLC)是最常见的肺部恶性肿瘤,预后较差。目前,从包含极性和非极性分子的多种生物标志物角度,仍然没有有效的肺癌诊断策略。为了从内源性分子水平探索 NSCLC 的病理变化,并进一步建立 NSCLC 疗效鉴定和监测的策略,我们对 NSCLC 患者进行了靶向代谢组学和脂质组学研究。基于 LC-MS/MS,定量测定了极性代谢物,包括 21 种氨基酸、7 种嘌呤、6 种三羧酸(TCA)循环代谢物,以及非极性脂质,如磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、溶血磷脂酰胆碱(LPC)、溶血磷脂酰乙醇胺(LPE)、鞘磷脂(SM)和神经酰胺(Cer)、二酰基甘油(DG)、三酰基甘油(TG),考虑到它们的代谢在前研究中与肺癌的发生密切相关。结果表明,14 种极性代谢物和 16 种脂质在 NSCLC 患者的血浆中明显改变,其中,经过多元统计分析,LPC 18:0(sn-2)、L-苯丙氨酸(Phe)、草酰乙酸(OAA)和黄嘌呤(XA)被筛选为 NSCLC 的潜在小分子和脂质生物标志物。此外,还提出了一种新的制定 NSCLC 识别方程的策略,并通过对 NSCLC 患者进行康艾注射液治疗成功进行了临床效用评估。总之,本研究从内源性极性和非极性分子的角度探讨了 NSCLC 的病理变化,为 NSCLC 的鉴定提供了思路。

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