Metabolomic Profiling of Blood-Derived Microvesicles in Breast Cancer Patients

Abstract

Malignant cells differ from benign ones in their metabolome and it is largely unknown whether this difference is reflected in the metabolic profile of their microvesicles (MV), which are secreted into the blood of cancer patients. Here, they are present together with MV from the various blood and endothelial cells. Harvesting MV from 78 breast cancer patients (BC) and 30 controls, we characterized the whole blood MV metabolome using targeted and untargeted mass spectrometry. Especially (lyso)-phosphatidylcholines and sphingomyelins were detected in a relevant abundance. Eight metabolites showed a significant discriminatory power between BC and controls. High concentrations of lysoPCaC26:0 and PCaaC38:5 were associated with shorter overall survival. Comparing BC subtype-specific metabolome profiles, 24 metabolites were differentially expressed between luminal A and luminal B. Pathway analysis revealed alterations in the glycerophospholipid metabolism for the whole cancer cohort and in the ether lipid metabolism for the molecular subtype luminal B. Although this mixture of blood-derived MV contains only a minor number of tumor MV, a combination of metabolites was identified that distinguished between BC and controls as well as between molecular subtypes, and was predictive for overall survival. This suggests that these metabolites represent promising biomarkers and, moreover, that they may be functionally relevant for tumor progression.

Circulating Carnitine Levels and Breast Cancer: A Matched Retrospective Case-Control Study

“…Park et al and Rashed et al found that plasma metabolites, including l-octanoylcarnitine, 5oxoproline, hypoxanthine, and docosahexaenoic acid, could be potential biomarkers for diagnosing breast cancer (6,7). Because metabolites are suggested to be related to the progression of breast cancer, they may be useful for preventing and treating breast cancer (8)(9)(10)(11).…”

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

“…45 Furthermore, EVs participate in the induction of angiogenesis, regulating immune responses and forming a premetastatic niche to promote cancer-targeted metastasis. [46][47][48][49][50] The vesicles have been confirmed to carry out intrinsic metabolic reactions. Fonseca et al have pointed out that nanoparticles are capable of glycolysis through internal metabolic enzymes to synthesize adenosine triphosphate.…”

“…There is just one study performed on the identification, diagnosis, and prognosis of breast cancer. 47 …”

“… 70 For serum-derived EVs are notable in bipolar disorder, 73 COVID-19, 74 Alzheimer’s disease, 50 , 75 The whole blood has been displayed on breast cancer. 47 Urine tissue are always applied to research on kidney and prostate, such as salt-sensitive hypertension, 78 and prostate cancer (PCa). 79 Auditory cell-derived EVs has been utilized in drug- and noise-related hearing loss.…”

“…The lipid molecules not only differentiate breast cancer patients from controls but also evaluate the future prognosis. 43 , 47 Pancreatic cancer is a highly malignant tumor with poor prognosis due to the difficulties in achieving early diagnosis. EVs monitoring 61 clinical serum samples by LC-MS untargeted metabolomics have identified Lyso phosphatidylcholine (PC) 22:0, PC (P-14:0/22:2) and phosphatidylethanolamine (PE) (16:0/18:1).…”