Гистологические и молекулярные особенности опухолевой пластичности рака желудка при сахарном диабете: ОРИГИНАЛЬНЫЕ СТАТЬИ

Сергей Игоревич  Пацкань; Юрий Игоревич  Стрельченко; Екатерина Валерьевна  Прокопенко; Анастасия Сергеевна  Гудёнова

doi:10.56871/PED.2026.34.20.004

Histological and molecular characteristics of tumor plasticity in gastric cancer with diabetes mellitus

ORIGINAL STUDIES

Sergey I. Patskan G.V. Bondar Republican Oncology Center https://orcid.org/0009-0004-4012-9500
Yuri I. Strelchenko Donetsk State Medical University named after M. Gorky https://orcid.org/0009-0009-3154-5509
Ekaterina V. Prokopenko Donetsk State Medical University named after M. Gorky https://orcid.org/0009-0008-7730-501X
Anastasia S. Gudenova Donetsk State Medical University named after M. Gorky https://orcid.org/0009-0008-8884-1969

Keywords:

gastric cancer tumor plasticity IGF-1R signaling thymidine phosphorylase diabetes mellitus рак желудка опухолевая пластичность сигналинг IGF-1R тимидинфосфорилаза сахарный диабет

Abstract

Background.Tumor plasticity in gastric cancer is a key determinant of the ability of tumor cells to undergo metabolic adaptation, invasion, and the development of resistance to anticancer therapy. Its implementation is driven by the coordinated activation of signaling–metabolic and microenvironmental networks, including various growth factors, angiogenesis, and stromal remodeling. These processes are significantly influenced by both the histological type of the tumor and comorbid conditions, including diabetes mellitus, which can modify tumor metabolism and the tumor microenvironment.

Aim.To assess the impact of histological type and diabetes mellitus on signaling–metabolic and microenvironmental mechanisms of tumor plasticity in gastric cancer.

Materials and methods.A total of 112 patients with gastric adenocarcinoma were examined and divided into four groups according to Lauren histological classification (intestinal and diffuse types) and the presence of diabetes mellitus. The expression of IGF-1R, thymidine phosphorylase (TP), TGF-β1, VEGF-A, and Ki-67 was assessed by immunohistochemistry with subsequent quantitative evaluation (H-score and percentage of positive cells). Statistical analysis was performed with consideration of intergroup differences.

Results.Patients with diabetes mellitus demonstrated a significant increase in the expression of IGF-1R, TP, TGF-β1, and VEGF-A regardless of histological type, indicating activation of proliferative, angiogenic, and microenvironmental signaling pathways. Ki-67 expression did not differ between the groups. The diffuse type of gastric cancer was characterized by a more pronounced activation of angiogenic-stromal interactions compared with the intestinal type.

Conclusions.Diabetes mellitus is associated with enhanced activation of signaling–metabolic and microenvironmental mechanisms underlying tumor plasticity in gastric cancer, contributing to the formation of an adaptive and invasive tumor phenotype. These findings highlight the importance of considering both the metabolic status of the patient and the histological type of the tumor when selecting therapeutic strategies and predicting disease outcomes.

Author Biographies

Sergey I. Patskan, G.V. Bondar Republican Oncology Center

Oncologist, Surgical Oncology Department No. 10, G.V. Bondar Republican Oncology Center, Donetsk People's Republic, Donetsk, Russia

Yuri I. Strelchenko, Donetsk State Medical University named after M. Gorky

MD, Ph D, Dr Med Sci,Associate Professor, Professor of the Department of Pathological Physiology named after Prof. N.N. Tranquilitati, Donetsk State Medical University named after M. Gorky, Donetsk People's Republic, Donetsk, Russia

Ekaterina V. Prokopenko, Donetsk State Medical University named after M. Gorky

5-th year student, Medical Faculty No. 2, Donetsk State Medical University named after M. Gorky; address: 16 Ilyicha ave., Donetsk, Donetsk People's Republic, 283003, Russia

Anastasia S. Gudenova, Donetsk State Medical University named after M. Gorky

6-th year student, Pediatric Faculty,Donetsk State Medical University named after M. Gorky, Donetsk, Russia

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