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采用 LC-MS/MS 技术对浸润性导管乳腺癌患者血清进行代谢组学研究。

Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach.

机构信息

Zanjan Metabolic Diseases Research Center, 48539Zanjan University of Medical Sciences, Zanjan, Iran.

Proteomics Research Center, 556492Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Int J Biol Markers. 2022 Dec;37(4):349-359. doi: 10.1177/03936155221123343. Epub 2022 Sep 27.

Abstract

BACKGROUND

Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2.

METHODS

An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis.

RESULTS

The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.

CONCLUSIONS

Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.

摘要

背景

浸润性导管癌(IDC)是最常见的乳腺癌类型,因此早期发现可显著降低死亡率。然而,IDC 的预后因素并不充分,我们需要新的标志物来治疗不同的个体。尽管正电子发射断层扫描和磁共振成像技术可用,但它们基于形态特征,无法提供癌症进展伴随的分子事件的任何线索。近年来,“组学”方法已被广泛开发,以提出癌症的新分子特征作为潜在的生物标志物,特别是在生物流体中。因此,进行了基于质谱的代谢组学研究,以寻找一些 IDC 的潜在代谢物标志物和与雌激素受体、孕激素受体、淋巴血管侵犯和人表皮生长因子受体 2 相关的具有预后价值的潜在代谢物。

方法

通过液相色谱-串联质谱(LC-MS/MS)对 IDC 患者进行非靶向代谢组学研究。XCMS 在线的多元主成分分析构建了一个能够分离研究组并定义显著改变的 m/z 参数的模型。还通过途径富集分析确定了最重要的生物学途径。

结果

结果表明,IDC 血清样本中明显改变的代谢物主要属于氨基酸和脂质。最重要的涉及途径包括精氨酸和脯氨酸代谢、甘油磷脂代谢以及苯丙氨酸、酪氨酸和色氨酸生物合成。

结论

与健康对照组相比,IDC 血清样本中明显改变的代谢物可能会在使用其他方法和在大样本中得到确认后,导致基于代谢物的潜在生物标志物的发展。

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