FEATURES OF THE GASTRIC CANCER MICROENVIRONMENT IN OVERWEIGHT PATIENTS

Ganusevich I.I., Bubnovska L.M., Vyskirko S.I., Burlaka A.P.

• R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

Obesity (Ob) increases the risk of malignant tumors development and worsens the course of the disease. The study of Ob in the oncological clinical practice requires the study of both adipose tissue and its impact on the tumor; so identifying factors of the tumor microenvironment associated with Ob will provide prospects for their use as markers of the tumor progression course in overweight patients. Objective: to identify the connection between different microenvironment parameters of gastric cancer (GC) (the rate of superoxide radicals (SR) generation, the hypoxia stages, the microvessels density (MVD), the activity of matrix metalloproteinases-2 and -9 (MMP-2 and -9), the number of tumor-associated macrophages (TAM), and tumor-infiltrating lymphocytes (TIL)) and the body mass index (BMI) of patients. Methods: clinical examination, EPR spectrometry, NMR spectroscopy, zymography in polyacrylamide gel, immunohistochemical, statistical. Results: in the tumor tissue of patients with gastric cancer and I–III degrees Ob, the level of SR generation was 2-times higher and the level of total gelatinase activity (MMP-2 and -9) was 1.4-times higher than in patients with normal body weight. The moderate and deep hypoxia of tumor tissue was observed more often among overweight (BMI > 25 kg/m²) gastric cancer patients than among normal weight (BMI < 25 kg/m²) patients. In the breast tissue of overweight patients (BMI > 25 kg/m²), the number of TAM was 1.4-times significantly higher and the level of TIL (T-lymphocytes) was 1.8-times significantly lower than in non-obese patients (BMI < 25 kg/m²). In tumors of middle-aged patients, there were found correlations between BMI and several indices: MVD, number of TAM and TIL (T-lymphocytes). Conclusion: the high values of BMI are associated with the increased pro-tumor characteristics of gastric cancer microenvironment, which indicates the influence of dysfunctional adipose tissue on tumor progression in the Ob and opens the possibility to study these factors of tumor microenvironment as markers of the gastric cancer course in overweight patients.