Exosomal Proteasome Levels as a Potential Biomarker for Differentiating Mastopathy from Breast Cancer via Liquid Biopsy

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Abstract

Introduction. Breast cancer (BC) remains the most prevalent malignancy among women worldwide. Limitations in mammography and ultrasound sensitivity, combined with the absence of reliable biomarkers for distinguishing benign from malignant breast lesions, frequently result in unnecessary biopsies and patient distress. Aim. To quantify 20S proteasome levels within blood-derived exosomes from patients with mastopathy and BC. Materials and Methods. The study included blood samples from clinically healthy women (n = 20), patients with diffuse dyshormonal breast dysplasia (n = 20), and BC patients (T1N0M0, n = 20). Exosomes were isolated from plasma and whole blood via ultracentrifugation and characterized using flow cytometry and nanoparticle tracking analysis. Following comprehensive exosomal protein profiling, 20S proteasome levels were quantified through Western blot analysis. levels were quantified through Western blot analysis. Results. 20S proteasomes within exosomes demonstrated neither chymotrypsin-like nor caspase-like enzymatic activity. However, their expression levels were significantly elevated in both plasma and whole blood exosomes from BC patients, with whole blood exosomes showing higher concentrations than plasma-derived exosomes. These findings suggest BC progression involves intercellular transfer of 20S proteasome subunits via blood exosomes from donor to recipient cells. Conclusion. Quantification of 20S proteasome levels in circulating exosomes shows potential for differentiating between benign and malignant breast diseases.

About the authors

S. N. Tamkovich

Federal State Budget Institution «Institute of Oncology and Neurosurgery, E.N. Meshalkin National Medical Research Center, Ministry of Healthcare of the Russian Federation; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Institute of Medicine and Medical Technologies, Novosibirsk State University

Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0001-7774-943X
SPIN-code: 6462-3700
Scopus Author ID: 7801643574
ResearcherId: G-9790-2013
Novosibirsk, the Russian Federation

N. V. Yunusova

Cancer Research Institute, Tomsk National Research Medical Center

Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0003-4595-4177
SPIN-code: 3513-1888
Scopus Author ID: 558006
Tomsk, the Russian Federation

D. A. Svarovsky

Cancer Research Institute, Tomsk National Research Medical Center

Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0002-8985-009X
SPIN-code: 4131-8608
Scopus Author ID: 57417248900
Tomsk, the Russian Federation

T. A. Shtam

National Research Center “Kurchatov Institute”

Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0003-0651-4785
SPIN-code: 3738-8187
Scopus Author ID: 95878
Gatchina, Leningrad Region, the Russian Federation

I. V. Kondakova

Cancer Research Institute, Tomsk National Research Medical Center

Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0002-0947-8778
SPIN-code: 9338-4149
Scopus Author ID: 349081
Tomsk, the Russian Federation

A. L. Chernyshova

Federal State Budget Institution «Institute of Oncology and Neurosurgery, E.N. Meshalkin National Medical Research Center, Ministry of Healthcare of the Russian Federation; Institute of Medicine and Medical Technologies, Novosibirsk State University

Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0002-8194-2811
SPIN-code: 2522-7513
Scopus Author ID: 557924
ResearcherId: C-8608-2012
Novosibirsk, the Russian Federation

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