Metabolomic Profiling of Plasma and Urine of Benzo(a)pyrene-Induced Mouse Models of Lung Cancer

IF 1.8 3区 化学 Q4 BIOCHEMICAL RESEARCH METHODS
Nitin Bhardwaj, Ashutosh Singh,  Rambabu
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Abstract

Background

Lung cancer (LC) is one of the most common malignancies with a high fatality rate. The current study recognizes the important metabolites and metabolic pathways in the plasma and urine of a BaP-induced mice model of LC.

Methods and Results

LC was generated by administering BaP (50-mg/kg body weight, twice a week for 1 month) orally. Plasma and urine samples were collected after 4 months of BaP treatment and derivatized with BSTFA and 1% TMCS. The metabolomics analysis was performed by using the gas chromatography mass spectrometry (GC–MS), and metabolites were recognized by annotating the peaks with the NIST mass spectra. There were 19 compounds in plasma and 48 compounds in urine, belonging to amino acids, fatty acids, sugars, and some organic categories, showing significant metabolic perturbations. The PCA and PLS-DA models also suggest a perfect discrimination between the metabolites in the plasma and urine of control and tumor-bearing mice. The VIP plot identifies nine compounds in plasma and in urine with maximum VIP scores. The maximum AUC value compounds in plasma (trimethyl phosphate, L-isoleucine, L-proline, 3,3′-oxydipropanol, L-glutamic acid, and 9-octadecenoic acid) and in urine (glycine, L-aspartic acid, L-5-oxoproline, butanedioic acid, glyceric acid, and butanoic acid) could be used as potential diagnostic markers in LC.

Conclusions

The metabolomics profiling of plasma and urine suggests a significant alteration in the relative abundance of fatty acids, sugars, and amino acids as well as potential biomarkers for the detection of LC.

苯并(a)芘诱导肺癌小鼠模型血浆和尿液代谢组学分析。
背景:肺癌(LC)是最常见的恶性肿瘤之一,死亡率高。目前的研究确认了bap诱导的LC小鼠模型血浆和尿液中的重要代谢物和代谢途径。方法和结果:采用BaP (50 mg/kg体重,每周2次,连续1个月)口服产生LC。BaP治疗4个月后收集血浆和尿液样本,用BSTFA和1% TMCS衍生化。代谢组学分析采用气相色谱-质谱(GC-MS)进行,代谢物通过NIST质谱标注峰来识别。血浆中有19种化合物,尿液中有48种化合物,属于氨基酸、脂肪酸、糖和一些有机类别,显示出明显的代谢扰动。PCA和PLS-DA模型还表明,对照小鼠和荷瘤小鼠血浆和尿液中的代谢物具有很好的区别。VIP图确定了血浆和尿液中VIP评分最高的9种化合物。血浆中(磷酸三甲酯、l -异亮氨酸、l -脯氨酸、3,3′-氧二丙醇、l -谷氨酸和9-十八烯酸)和尿液中(甘氨酸、l -天冬氨酸、l -5-氧脯氨酸、丁二酸、甘油酸和丁酸)的最大AUC值可作为LC的潜在诊断指标。结论:血浆和尿液的代谢组学分析表明,脂肪酸、糖和氨基酸的相对丰度以及LC检测的潜在生物标志物发生了显著变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
219
审稿时长
2.6 months
期刊介绍: Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.
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