Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a fol

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Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a follow‑up study Anna Synakiewicz1 · Anna Stanislawska‑Sachadyn2 · Malgorzata Sawicka‑Zukowska3 · Grazyna Galezowska4 · Joanna Ratajczyk4 · Anna Owczarzak5 · Malgorzata Skuza6 · Lidia Wolska4 · Teresa Stachowicz‑Stencel1  Received: 13 May 2020 / Accepted: 1 November 2020 © The Author(s) 2020

Abstract Amino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing to controls. Results suggest that plasma free AA profile may serve as a prognostic biomarker. Keywords  Amino acid profile · Metabolomics · Cancer · Tumor biomarkers

Introduction Amino acids (AAs) as metabolic key regulators of many cell pathways are essential for differentiation, growth and maintenance of immunological balance of human cells. Handling editor: G. J. Peters Electronic supplementary material  The online version of this article (doi:https​://doi.org/10.1007/s0072​6-020-02910​-8) contains supplementary material, which is available to authorized users. * Teresa Stachowicz‑Stencel [email protected] 1

A cachectic oncological patient commonly presents hypermetabolism with intensified processes of lipolysis, fatty acid oxidation and gluconeogenesis, as well as protein catabolism (Bernstein and Ortiz 2005; Giovannucci 1999). Studies on amino acids carried out on animal cancer models have shown an increased protein catabolism in muscle cells with a simultaneous decrease in their synthesis and an increase in total protein turnover compared to control group (Kawamura et al. 1982). Our previous research concerning plasma-free amino acid (PFAA) profile in pediatric oncological patients at the time of diagnosis showed significant differences in PFAA levels between pediatric cancer patients and control group (Synakiewicz et al. 2017). In the current research, we additionally included post-treatment data to find out the severity of changes and its tendency to recur to normal values. We made an attempt to establish if PFAAs may serve as prognostic biomarkers.



Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 7 Debinki Street, 80‑211, Gdansk, Poland

2



Department of Molecular Biotechnology and Microbiology, Gdansk University of Technology, Gdansk, Poland

3

Department of Pediatric Oncology and Hematology, Medical University of Bialystok, Bialystok, Poland

Materials and methods

4

Department of Environmental Toxicology, Medical University of Gdansk, Gdansk, Poland

Patients

5

Department of Clinical Nutrition, Medical University of Gdansk, Gdansk, Poland

6

Diagnostic Imaging Department, The Polish Red Cross Marit