Changes in the metabolism of axillary lymph node cells as a predictor of regional metastasis in breast cancer

doi:10.5493/wjem.125128

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World Journal of Experimental Medicine

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2220-315X

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Exp Med. Sep 20, 2026; 16(3): 125128
Published online Sep 20, 2026. doi: 10.5493/wjem.125128

Changes in the metabolism of axillary lymph node cells as a predictor of regional metastasis in breast cancer

Marina A Senchukova, Azamat T Ishemgulov, Sergey N Letuta, Natalia V Saidler, Dmitry G Tagabilev

Marina A Senchukova, Dmitry G Tagabilev, Scientific and Clinical Center No. 3, Petrovsky National Research Centre of Surgery, Moscow 108840, Troitsk, Russia

Azamat T Ishemgulov, Sergey N Letuta, Department of Biophysics, Orenburg State University, Orenburg 460018, Russia

Natalia V Saidler, Department of Pathology, Orenburg Regional Cancer Clinic, Orenburg 460021, Orenburgskaya Oblast’, Russia

Author contributions: Senchukova MA formulated the idea and aims of the study, wrote the first version of the manuscript and performed the analysis of the results and statistical processing of the results; Saidler NV made a significant contribution to the development of the study methodology, participated in the preparation of tables and figures; Ishemgulov AT designed and performed all the experiments with the determination of delayed luminescence of erythrosine (DLE) in breast tissue; Letuta SN upended the experiments to determine the DLE in breast tissues and participated in the discussion of the research results; and Tagabilev DG participated in the discussion of the obtained results and helped to revise the manuscript. All the authors wrote and approved the final version of the manuscript.

AI contribution statement: The authors did not use any AI tool in preparing this manuscript.

Supported by Russian Science Foundation, No. 23-25-00183.

Institutional review board statement: Ethical approval was obtained from the Ethics Committee of Orenburg State Medical University (No. 311, dated January 13, 2023).

Clinical trial registration statement: The study does not require registration as it does not meet the definition of a clinical trial.

Informed consent statement: All patients provided written informed consent to participate in the clinical study.

Conflict-of-interest statement: The authors (Azamat T Ishemgulov, Marina A Senchukova, Sergey N Letuta and Natalia V Saydler) declare the existence of a patent interest: "Method for detecting tumor tissue in surgical material for breast cancer." Patent number RU 2835219 C1 02/25/2025.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Corresponding author: Marina A Senchukova, Scientific and Clinical Center No. 3, Petrovsky National Research Centre of Surgery, Oktyabrsky Prospekt, 3, Moscow 108840, Troitsk, Russia. masenchukova@yandex.com

Received: July 1, 2026
Revised: August 3, 2026
Accepted: August 28, 2026
Published online: September 20, 2026
Processing time: 83 Days and 3.6 Hours

Abstract

BACKGROUND

Recent studies have shown that the delayed luminescence of erythrosine (DLE) indicators differs between tumor and nontumor breast tissue in patients with breast cancer (BC).

AIM

To study the features of metabolism of axillary lymph node (ALN) cells and their relationship with regional metastasis in BC patients.

METHODS

This prospective, single-center, observational cohort study included 69 patients with newly diagnosed BC. DLE indicators were measured for 152 ALNs. DLE decay kinetics were recorded using flash photolysis. A control circuit interfaced the analog measuring devices and digital data processing systems. Eighty-eight and 74 ALN samples were stained with antibodies against vascular cell adhesion molecule-1 (VCAM-1) and C-X-C motif chemokine receptor 4 (CXCR4), respectively. Statistical calculations were performed using Statistica version 12.0 software.

RESULTS

Singlet oxygen-sensitized delayed fluorescence (SOSDF) indicators were significantly lower, whereas phosphorescence and thermally activated delayed fluorescence indicators were significantly higher in ALNs with metastases than in those without metastases (P < 0.0001). Pronounced VCAM-1 expression in ALNs was significantly more common in patients with tumor grade 3 and human epidermal growth factor receptor 2 (HER2) overexpression and in patients with HER2-positive BC. Pronounced CXCR4 expression in lymph node (LN) follicles was detected significantly more often in patients with metastases in ALNs and with lymphovascular invasion. The intensity of delayed phosphorescence positively correlated with both VCAM-1 and CXCR4 expression in the LN follicles, and VCAM-1 expression in the LN follicles was negatively correlated with SOSDF and positively correlated with the duration of delayed phosphorescence.

CONCLUSION

These results indicate that metastatic LNs exhibit greater oxygen consumption by tumor cells and that changes in tumor cell metabolism are associated with increased CXCR4 and VCAM-1 expression in ALNs.

Keywords: Breast cancer; C-X-C motif chemokine receptor 4; Delayed fluorescence of erythrosine; Lymph node metastases; Singlet oxygen-sensitized delayed fluorescence; Vascular cell adhesion molecule-1

Core Tip: We studied the delayed luminescence of erythrosine indicators and the expression of vascular cell adhesion molecule-1 (VCAM-1) and C-X-C motif chemokine receptor 4 (CXCR4) in axillary lymph nodes (LN) from patients with breast cancer. The results indicated that metastatic LNs exhibit greater oxygen consumption by tumor cells and that changes in tumor cell metabolism are associated with increased CXCR4 and VCAM-1 expression in axillary LNs.