NMR-Based Metabolomic Analysis of Serum and Interstitial Fluid from Patients with Breast Cancer-Related Lymphedema

Background: Breast cancer-related lymphedema (BCRL) is a serious complication often occurring after breast cancer surgery, which substantially diminishes the quality of life for those affected. Current treatments, including conservative and surgical approaches, primarily address lymphedema symptoms, slow disease progression, and mitigate complications. Therefore, there is an urgent need for new and effective methods for early diagnosis and treatment of BCRL. Methods: In the current study, we analyzed human serum and interstitial fluid (ISF) from BCRL patients without cancer progression (n = 22, age 69.6 ± 3.4 years). Control blood samples were collected from age-matched individuals without BCRL (n = 12, age 63.7 ± 6.5 years). Quantitative metabolomic profiling of the samples was performed using a high-frequency 1H NMR, and the concentrations (in μM) of a total of 48 metabolites in the samples were determined. Results: Serum and ISF in BCRL patients display a similar metabolomic composition: concentrations of most metabolites are similar or comparable. At the same time, the concentrations of pyruvic acid, 2-ketoisovaleric acid, ketoleucine, 3-methyl-2-oxovaleric acid, tryptophan, proline, creatine, isobutyric acid, propylene glycol, ascorbic acid, formic acid, isoleucine, leucine, threonine, and creatinine are higher in serum of BCRL patients compared to controls. Quantitative metabolite set enrichment analysis (QMSEA) of serum samples from BCRL patients and controls indicates that the most affected metabolic pathways involve energy production and inflammation. Conclusions: Differential serum metabolites reported in this study can be considered potential biomarkers for lymphedema.