Метаболомная подпись свободных муцинов при онкологических заболеваниях: CA125 и рак яичников высокой степени злокачественности

Vv Chagovets,Oa Mayboroda,Nl Starodubtseva,Sv Pavlovich,Gn Khabas,Vg Vasil'Ev,Mv Iurova

doi:10.24075/brsmu.2021.065

Abstract

Mucins are large glycoproteins characterized by the abundant O-linked oligosaccharides (O-glycans) clustered on a protein backbone. Most of the circulating mucins are rapidly cleared by glycan-recognizing hepatic clearance receptors in the liver. Those mucins that remain in the bloodstream are most commonly used as markers in clinical diagnostics. One of such circulating mucins is MUC16; a peptide epitope of which is known as CA125 antigen — a marker for ovarian cancer. Here, using a targeted 1H-NMR profiling of plasma we are exploring a link between the measured CA125 values and the systemic metabolism of the patients within a group with confirmed high-grade ovarian cancer. The study allowed identifying statistically significant associations between the measured values of CA125 epitope and the plasma concentrations of glucose, glutamine, alanine, betaine and serine. The significance of the identified associations for the listed compounds is below 0.01. This, in turn, enables us to hypothesize about a possibility of including the metabolic measures into a composite score of the ovarian cancer based on the CA125 epitope of MUC16.

Highlights

IntroductionAuthor contribution: Chagovets VV — study planning, sample preparation, discussion of NMR data processing, manuscript authoring and editing; Vasil'ev VG — sample preparation, NMR analysis; Iurova MV, Khabas GN — collection and characterization of clinical samples, discussion of the results; Pavlovich SV — study research, discussion of the results; Starodubtseva NL — study planning, clinical data processing; Mayboroda OA — study planning and management, manuscript authoring, NMR data processing
We address a different question, namely to which extend the CA125 values can be associated with a metabolic status of the patients
The main goal of this study is to explore the associations between the measured values of CA125 and concentrations of plasma metabolites within a homogeneous group of the patients with clinically confirmed high grade ovarian cancer

Summary

Introduction

Author contribution: Chagovets VV — study planning, sample preparation, discussion of NMR data processing, manuscript authoring and editing; Vasil'ev VG — sample preparation, NMR analysis; Iurova MV, Khabas GN — collection and characterization of clinical samples, discussion of the results; Pavlovich SV — study research, discussion of the results; Starodubtseva NL — study planning, clinical data processing; Mayboroda OA — study planning and management, manuscript authoring, NMR data processing. Пептидный эпитоп одного из таких циркулирующих муцинов, называемого MUC16, известен как антиген СА125, маркер рака яичников. Целью работы было провести профилирование метаболитов плазмы с помощью 1H-ЯМР анализа и изучить связь между измеренными значениями CA125 и системным метаболизмом пациентов в группе с подтвержденным раком яичников высокой степени злокачественности. В. Чаговец — планирование исследования, подготовка образцов, обсуждение обработки данных ЯМР, написание и редактирование рукописи; В. В. Павлович — планирование исследования, обсуждение результатов; Н. Л. Стародубцева — планирование исследования, обработка клинических данных; О. А. Майборода — планирование исследования и руководство им, написание рукописи, обработка данных ЯМР

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