Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study

Abstract

Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ®) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved onecarbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.

Early Breast Cancer Detection Using Untargeted and Targeted Metabolomics

“…Some other findings of the current study have also been reported by previous literature . For instance, galactose metabolism is known to influence mitochondrial dysfunction and cancer growth in human BC cells and is also an early indicator of other gynecological cancers. − Moreover, recent comparative studies have identified decreases in glycine, serine, and threonine to be indicative of the metastatic potential of EBC and subsequent risk of invasive ductal carcinoma . In the current study, the levels of all three metabolites were significantly reduced ( p < 0.05) in EBC patients (see Figure ).…”

“…57−59 Moreover, recent comparative studies have identified decreases in glycine, serine, and threonine to be indicative of the metastatic potential of EBC 31 and subsequent risk of invasive ductal carcinoma. 60 In the current study, the levels of all three metabolites were significantly reduced (p < 0.05) in EBC patients (see Figure 4). Finally, our results show significant disturbances in glutamate and glutamine metabolism, a finding that is well-known in cancer research.…”

Decoding the Gene Regulatory Network of Muscle Stem Cells in Mouse Duchenne Muscular Dystrophy: Revelations from Single-Nuclei RNA Sequencing Analysis

“…Analysis of "scMetabolism" indicated that MuSCs from DMD mut muscles had higher activities of oxidative phosphorylation (OXPHOS), citric acid cycle (TCA cycle), glycolysis metabolism, and pentose phosphate pathway (PPP) activities compared to MuSCs from control muscles (Figure 6); (2) Purines and pyrimidines are fundamental building blocks of nucleotides, which are crucial for cell proliferation. Proliferative cells require nucleotides, including purines and pyrimidines for synthesizing cellular components [16]. When there is a dysregulation in purine and pyrimidine metabolism, there is an increase in DNA damage and cell turnover [17].…”

Identification of Potential Biomarkers and Metabolic Changes in the Serum of Breast Lump Patients Among Kelantanese Based on 1H NMR Metabolomics

“…Nuclear magnetic resonance ( 1 H NMR) spectroscopy-based metabolomics method is one of the powerful analytical techniques employed to study the metabolic profile of a wide range of biological samples, such as serum, faecal and urine, which require only a minimal amount of samples [24,25] . Several published studies have proved the utility of metabolic profiles anaysed by 1 H NMR in the detection of breast cancer [26,27] . When analysing serum samples with 1 H NMR, Zhou et al [28] discovered that nine metabolites were substantially altered in breast cancer compared to healthy controls.…”