More Tushar H, RoyChoudhury Sourav, Christie Joel, Taunk Khushman, Mane Anupama, Santra Manas K, Chaudhury Koel, Rapole Srikanth
Proteomics Lab, National Center for Cell Science, Ganeshkhind, Pune 411007, MH, India.
Savitribai Phule Pune University, Ganeshkhind, Pune 411007, MH, India.
Oncotarget. 2017 Dec 23;9(2):2678-2696. doi: 10.18632/oncotarget.23626. eCollection 2018 Jan 5.
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.
浸润性导管癌(IDC)是最常见的乳腺癌类型,也是乳腺癌相关死亡的主要原因。在本研究中,使用靶向液相色谱多反应监测质谱法(LC-MRM/MS)和非靶向气相色谱质谱法(GC-MS)分析了72个组织样本和146个血清样本的代谢组学特征。单变量和多变量统计处理相结合,发现与对照组相比,IDC组织和血清样本中分别有42种和32种代谢物发生了显著变化。组织中一些代谢物的变化也反映在血清中,表明IDC中代谢物存在双向相互作用。此外,8种组织代谢物和9种血清代谢物从对照到良性再到IDC呈现出渐进性变化,表明它们在恶性转化中可能发挥作用。我们在组织和血清中鉴定出一组三种代谢物,即色氨酸、酪氨酸和肌酸,它们可用于从对照和良性个体中筛选出IDC患者。IDC中的代谢组学改变显示嘌呤和嘧啶代谢、氨基糖代谢、氨基酸代谢、脂肪酸生物合成等存在扰动。综合来看,本研究为IDC的代谢适应性提供了有价值的见解,有助于识别诊断标志物以及潜在的治疗靶点。