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

Abstract

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.

Application of metabolomics in the diagnosis of breast cancer: a systematic review

“…Tyrosine has the highest frequency with 12 hits in total, followed by alanine reported with 11 hits. In studies focusing on the tissue [16,18,36,37,40], most significant metabolites tended to be up-regulated except glucose. Notably, changes of some fatty acids like palmitic acid, linoleic acid and stearic acid were consistently increased in the blood.…”

“…Targeted and untargeted metabolomics both accounted for 6 articles ( Figure 5C). [15,27], plasma [17], tissue [18], saliva [42], urine [46] 6 plasma [9,34,41], serum [14,18,23] 2 Alanine 6 saliva [11,42], serum [15], plasma [21,41], urine [43] 5 plasma [9,34], serum [14], urine [22], serum&plasma [30] 3 Glutamic acid 6 serum [15], tissue [16,18], plasma [21], saliva [17,42] 4 plasma [9], serum [14], urine [22], serum&plasma[32] 4…”

“…Valine 4 saliva [11,42], serum [15], plasma [21] 6 plasma [9,17,24,34], serum [14], urine[22] 5 Phenylalanine 5 serum [15], tissue [18], saliva [26,42], urine […”

“…Former studies suggested that several decreased amino acids might be the result of excessive consumption or preferential utilization to sustain the uncontrolled growth of BC cells [18,22,24,27,42,47,51,68]. Based on clinical metabolomic studies, tyrosine and alanine shared the highest frequency with 12 hits, indicating they might be sensitive metabolites in the diagnosis of BC.…”

Serum metabolomic alterations in multiple myeloma revealed by targeted and untargeted metabolomics approaches: a pilot study

“…These metabolites were selected based on the previous literature survey of various cancer metabolomic studies. 22 The chromatography parameters and details of MRM library are discussed in our previous report 23 and the same have been utilized for this study as well. Metabolites extraction was executed by the addition of 200 mL methanol to 25 mL of every serum samples, vortexed vigorously and incubated at À20 C overnight.…”