Agnieszka Skorupa

NMR-based serum metabolomics in patients with low-differentiated serous ovarian cancer

In this pilot study the proton Nuclear Magnetic Resonance (¹H NMR)-based metabolomics was applied to explore the serum metabolomes of the patients with high-grade serous ovarian carcinoma (HGSOC) and the patients with benign gynaecological disease and to identify the characteristic biomarkers. We analyzed serum samples from 17 HGSOC patients and 14 control patients with benign gynecological conditions. Serum metabolites were profiled using 1H NMR spectroscopy, and multivariate data analyses, including Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were performed to identify discriminating metabolites. The multivariate analysis revealed the lower levels of the lipid compounds, choline, branched-chain amino acids, 3-hydroxybutyrate (3HB), acetoacetate, and the higher level of lactate in the sera of the HGSOC patients compared to the control group. NMR-based metabolomic analysis can serve as a supporting method for the detection of ovarian cancer and may be useful as an adjunct to molecular diagnostics.

Metabolomic Analysis of Histological Composition Variability of High-Grade Serous Ovarian Cancer Using 1H HR MAS NMR Spectroscopy

In this work, the HR MAS NMR (high-resolution magic-angle spinning nuclear magnetic resonance) spectroscopy technique was combined with standard histological examinations to investigate the metabolic features of high-grade serous ovarian cancer (HGSOC) with a special focus on the relation between a metabolic profile and a cancer cell fraction. The studied group consisted of 44 patients with HGSOC and 18 patients with benign ovarian tumors. Normal ovarian tissue was also excised from 13 control patients. The metabolic profiles of 138 tissue specimens were acquired on a Bruker Avance III 400 MHz spectrometer. The NMR spectra of the HGSOC samples could be discriminated from those acquired from the non-transformed tissue and were shown to depend on tumor purity. The most important features that differentiate the samples with a high fraction of cancer cells from the samples containing mainly fibrotic stroma are the increased intensities in the spectral regions corresponding to phosphocholine/glycerophosphocholine, phosphoethanolamine/serine, threonine, uridine nucleotides and/or uridine diphosphate (UDP) nucleotide sugars. Higher levels of glutamine, glutamate, acetate, lysine, alanine, leucine and isoleucine were detected in the desmoplastic stroma within the HGSOC lesions compared to the stroma of benign tumors. The HR MAS NMR analysis of the metabolic composition of the epithelial and stromal compartments within HGSOC contributes to a better understanding of the disease’s biology.