Spirina, L. V., Augustinovich , A. V., Barkysheva, A. A., Bogdanova, V. A., Afanas’ev, S. G., Svarovsky, D. A., & Yunusova , N. V. (2024). 20S Proteasomes, Hsp27 and LC3B Content in Plasma Exosomes of Gastric Cancer Patients, Association with Metabolic Disorders. Voprosy Onkologii, 70(5), 894–902. https://doi.org/10.37469/0507-3758-2024-70-5-894-902

Abstract

Introduction. Stomach cancer is one of the most common oncological diseases in Russia and worldwide. Early diagnosis of this pathology is an important issue. In recent years, studies have been conducted on the use of a non-invasive liquid biopsy for tumors of various localizations, which is easy to use and allows studying extracellular plasma vesicles. This is currently a promising area of modern molecular oncology.

Aim. To analyse the content of proteins 20S proteasomes, Hsp27 and LC3B in plasma exosomes in gastric cancer compared with exosomes isolated from patients with atrophic gastritis, taking into account metabolic disorders and obesity.

Materials and Methods. The study included 18 patients with gastric cancer treated in the clinics of the Cancer Research Institute, Tomsk NRMC. The control group consisted of 6 patients with atrophic gastritis. The patients were divided into groups according to the stage of the tumor. Tumor stage T1-2 was observed in 12 patients and T3-4 in 6 patients. Blood plasma exosomes were isolated by ultracentrifugation. The typing was done using a CD9 marker. The content of 20S proteasome, Hsp27 and LC3B proteins in plasma exosomes were determined by Western blotting.

Results. The study found that plasma exosomes containing 20S proteasomes and LC3B were 3.8 and 1.4 times higher in patients with gastric cancer compared to patients without tumor pathology (atrophic gastritis). At the same time, there was a 2.3-fold reduction in the level of Hsp27 in exosomes isolated from the patients' blood plasma. The study did not reveal the relationship between the stage of the tumor process and the content of 20S proteasomes in blood exosomes. However, an increase in the LC3B content in exosomes was associated with an increase in the stage of the tumor process.

Conclusion. The growth of 20S proteasomes and LC3B in plasma exosomes isolated from patients with gastric cancer was revealed. At the same time, the level of Hsp27 protein in exosomes was reduced in patients with malignant tumors. The relationship between LC3B protein levels and the stage of the tumor process was noted, which requires further investigation. The study developed and justified criteria for the use of liquid biopsy markers in risk stratification and diagnosis of gastric cancer. Metabolic disorders were identified as the main drivers of tumor progression, and their significance was emphasized.

https://doi.org/10.37469/0507-3758-2024-70-5-894-902

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