TUMOR MICROENVIRONMENT AND BODY MASS INDEX: CORRELATION WITH THE PROGRESSION OF GASTRIC CANCER


I. Ganusevich, A.M. Haleeva

RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

DOI: https://doi.org/10.15407/oncology.2023.03.214

 

Summary. Obesity increases the risk of developing malignant tumors contributes to the worsening of the progression of the disease. Today, the relationship between the course of gastric cancer (GC) and obesity is considered to have been proven, however the epidemiological data pertaining to this relationship is marked by contradictions and uncertainties. The identification of tumor microenvironment factors that are associated with obesity (taking into account the age and gender of patients) will allow to group patients in accordance to the risk of adverse progression of the disease. Aim: to determine the levels of the metastasis of regional and distant cancer as well as the survival of patients with GC depending on their body mass index (BMI), taking into account their age and gender; to analyze the correlation of these indicators to the aggressiveness of the tumor microenvironment, which was determined by us previously by grouping patients with GC by BMI, age and sex. Object and methods: the clinico-pathological indicators and the overall 3-year survival of 246 patients (171 men, 75 women) with primary esophageal cancer were studied using clinical, oncological and statistical methods. Results: it was found that there was no significant statistical difference (p > 0.05) between the frequency of the metastasis of distant cancer in the groups of patients, regardless of weight, sex and age. Patients with normal weight had a 1.4 times significantly higher (p = 0.012) frequency of regional cancer metastasis than patients with excess weight. Significantly highest survival rates were observed in middle-aged men of normal weight, elderly women of normal weight, and middle-aged women who were overweight/obese, there was no significant statistical difference (p > 0.05) between the frequency of distant cancer metastasis in the groups of patients regardless of weight, sex and age. Patients with normal weight had a 1.4 times significantly higher (p = 0.012) frequency of regional cancer metastasis than patients with excess weight. The highest survival rates were observed in middle-aged men of normal weight, elderly women of normal weight, and middle-aged women who were overweight/obese and the lowest in overweight/ obese middle-aged men and overweight/obese elderly women. It was determined that in cases of patients who were overweight, survival is correlated with the nature of aggressiveness of the tumor as it relates to the age and gender of the patients with GC (a high frequency of pro-tumor factors of the GC microenvironment is associated with low survival (direct negative correlation; k = –0.93)), as it relates to patients with normal weight — no correlation (direct positive correlation; correlation coefficient = 0.98). Conclusions: the study of tumor microenvironment factors that are associated with obesity, taking into account patients’ age and gender, will allow to group patients with GC according to the risk of adverse progression of the disease at the stage of initial tumor detection, and in a technically accessible and economical way, to improve the determination of a prognosis and the efficiency of anticancer therapy.

 

References

  1. Mastrocola MR, Roque SS, Benning LV, Stanford FC. Obesity education in medical schools, residencies, and fellowships throughout the world: a systematic review. Int J Obes 2020, 44: 269– doi: https://doi.org/10.1038/s41366-019-0453-6.
  2. WHO newsletter https://www.who.int/ru/news-room/fact-sheets/detail/obesity-and-overweight.
  3. Saitta C, Pollicino T, Raimondo G. Obesity and liver cancer. Ann Hepatol 2019, 18 (6): 810– doi: https://doi.org/10.1016/j.aohep.2019.07.004.
  4. Goossens GH, Blaak EE. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen. Front Endocrinol (Lausanne) 2015; 6: 55. doi: 10.3389/fendo.2015.00055.
  5. Colditz G, Peterson Obesity and cancer: evidence, impact, and future directions. Clinical Chemistry 2018; 64 (1): 154–62. doi: https://doi.org/10.1373/clinchem.2017.277376.
  6. Elliott JA, Reynolds JV. Visceral obesity, metabolic syndrome, and esophageal adenocarcinoma. Front Oncol 2021; 11: 627270. doi: 10.3389/fonc.2021.627270.
  7. Belladelli F, Montorsi F, Martini A. Metabolic syndrome, obesity and cancer risk. Curr Opin Urol 2022; 32 (6): 594-7. doi: 10.1097/MOU.0000000000001041.
  8. Li Y, Wang WB, Yang L, et al. The combination of body composition conditions and systemic inflammatory markers has prognostic value for patients with gastric cancer treated with adjuvant chemoradiotherapy. Nutrition 2022; 93: 111464. doi: 10.1016/j.nut.2021.111464.
  9. Fan X, Wang D, Zhang W, et al. Inflammatory markers predict survival in patients with advanced gastric and colorectal cancers receiving anti-PD-1 therapy. Front Cell Dev Biol 2021; 9: 638312. doi: 10.3389/fcell.2021.638312.
  10. Bubnovskaya L, Osinsky D. Tumor microenvironment and metabolic factors: contribution to gastric cancer. Exp Oncol 2020; 42 (1): 2–10. doi: 32471/exp-oncology.2312-8852.vol-42-no-1.14056.
  11. Chen Y, Zhang S, Wang Q, Zhang X. Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol 2017; 10 (1): 36. doi: https://doi.org/10.1186/s13045-017-0408-0.
  12. Carlomagno N, Incollingo P, Tammaro V, et al. Diagnostic, predictive, prognostic, and therapeutic molecular biomarkers in third millennium: a breakthrough in gastric cancer. BioMed Res Int 2017; 2017 (3): ID7869802. doi: https://doi.org/10.1155/2017/7869802.
  13. Chang WJ, Du Y, Zhao X. Inflammation-related factors predicting prognosis of gastric cancer. World J Gastroenterol 2014; 20 (16): 4586– doi: 10.3748/wjg.v20.i16.4586..
  14. Bibak F, Ahmadi S, Khateri Z, Ahmadi A, et al. The role of matrix metalloproteinase-2 expression in gastric cancer susceptibility: a systematic review. Int J Cancer Manag 2019; 12 (9): e94185. doi: https://dx.doi.org/10.5812/ijcm.94185.
  15. WHO mean body mass index (BMI). World Health Organization 2019, retrieved 5. https://www.who.int/europe/news-room/fact-sheets/item/a-healthy-lifestyle—who-recommendations.
  16. Blackburn H, Jacobs D. Commentary: origins and evolution of body mass index (BMI): continuing saga. Int J Epidemiol 2014; 43 (3): 665–9. doi: https://doi.org/10.1093/ije/dyu061.
  17. Nuttall FQ. Body mass index obesity, BMI, and health. Nutrition Research 2015; 50 (3): 117– doi: https://doi.org/10.1097/nt.0000000000000092.
  18. I. Ganusevich, L.M. Bubnovska, A.I. Goncharenko, A.P. Burlaka. Tumor microenvironment and body mass index in gastric cancer patients: formation of groups at risk of adverse course. Oncology 2022; 24 (2): 102–8. doi: 10.32471/oncology.2663-7928.t-24-2-2022-g.10456.
  19. De Clerk YA, Perez N, Shimada H, et al. Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer research 1992; 52 (3): 701– PMID: 1732058. https://pubmed.ncbi.nlm.nih.gov/1732058/.
  20. Vaupel P, Okunieff P, Kallinowski F, et al. Correlation between 31P-NMR spectroscopy and tissue O2 tention measurements in a murine fibrocarcoma. Radiation Res 1989; 120 (3): 477– PMID: 2594969. https://pubmed.ncbi.nlm.nih.gov/2594969/.
  21. Burlaka AP, Sidorik EP, Ganusevich II, et al. High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels. Exp Oncol 2006; 28 (4): 323–5. PMID: 17285119. https://pubmed.ncbi.nlm.nih.gov/17285119/.
  22. Kaikaew K, Grefhorst A, Visser JA. Sex differences in brown adipose tissue function: sex hormones, glucocorticoids, and their crosstalk. Front Endocrinol (Lausanne). 2021; 12: 652444. doi: 10.3389/fendo.2021.652444.
  23. Eaton SA, Sethi JK. Immunometabolic links between estrogen, adipose tissue and female reproductive metabolism. Biology (Basel) 2019; 8 (1): doi: 10.3390/biology8010008.
  24. Sebo ZL, Rodeheffer MS. Testosterone metabolites differentially regulate obesogenesis and fat distribution. Mol Metab 2021; 44: 101141. doi: 10.1016/j.molmet.2020.101141.

No comments » Add comment