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Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples

机译:乳腺浸润性导管癌的代谢组学改变:使用组织和血清样品的综合代谢组学研究

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摘要

Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets.
机译:浸润性导管癌(IDC)是最常见的乳腺癌类型,也是与乳腺癌相关的死亡率的主要原因。在本研究中,使用靶向液相色谱多反应监测质谱(LC-MRM / MS)和非靶向气相色谱质谱(GC-MS)方法分析了72个组织样品和146个血清样品的代谢组学谱。与对照组相比,单变量和多变量统计处理的结合分别确定了IDC组织和血清样品中42和32种代谢物的显着变化。来自组织的某些代谢物变化也反映在血清中,表明IDC中代谢物的双向相互作用。此外,8种组织代谢物和9种血清代谢物显示出从对照到良性再到IDC的逐渐变化,表明它们可能在恶性转化中发挥作用。我们确定了一组三个代谢物即。组织和血清中的色氨酸,酪氨酸和肌酸,可用于从对照和良性筛查IDC受试者。 IDC的代谢组学变化显示了嘌呤和嘧啶代谢,氨基糖代谢,氨基酸代谢,脂肪酸生物合成等方面的紊乱。综合而言,本研究为IDC的代谢适应提供了有价值的见解,可帮助鉴定诊断标志物和潜力治疗目标。

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