Despite the recent advances in the diagnostic and therapeutic tactics of patients with bladder cancer, the relevance of this oncological problem remains problematic up to now. Angiogenesis is one of the main factors in the survival and spread of tumor cells. At the moment, there is a wealth of evidence confirming the involvement of growth factors, in particular, VEGF (vascular endothelial growth factor) and TNF (tumor necrosis factor) responsible for the mitogenic activity of cells in the development and progression of malignancies and, therefore, are promising targets when using targeted therapy. The purpose of the study was to determine the molecular markers of VEGF, TNF-α and TNF-β in the urine of patients with bladder cancer stage T3N0M0 and to establish their relation to the degree of G neoplasia. Material and methods. The study included 47 patients with bladder cancer stage T3N0M0 (main group). There were 27 men and 20 women among them. The age of men was 58.17.8 and women – 59.4 1.3 years. Clinical data from 30 healthy individuals were used as control group data. Results and discussion. According to the results of the statistical analysis, patients with bladder cancer stage T3N0M0 had the average level of VEGF in urine 245.657.90 pg / ml which significantly exceeded this indicator in the control group, which was 131.237.80 pg / ml. However, this difference was statistically significant (p = 0.04). When studying the level of VEGF in the urine of patients with degrees of neoplasia G1, G2, G3, we found out that in the mentioned subgroups of patients, its average value was 239.59 9.84 pg / ml, 246.848.79 pg / ml and 251.577.22 pg / ml, respectively. We observed a low degree of G1 neoplasia more frequently. It was detected in 19 of 47 patients, accounting for 40.43%. G1 was diagnosed in 34.04% of patients, and G3 in 25.53% of bladder cancer patients in stage T3N0M0. It should be emphasized that due to the retrospective nature of the study, the above data did not fully reflect the actual epidemiological situation regarding the incidence of T3N0M0 stage bladder neoplasia. The data obtained during the study on the levels of TNF- in the urine of patients with bladder cancer in stage T3N0M0 had no fundamental differences from the results obtained in the study of stages T1 and T2: the average level of TNF- in the urine was 361.516.76 pg / ml and 352.686.75 pg / ml in the control group. This difference was not statistically significant (p> 0.05). When determining TNF- level in patients with different degrees of neoplasia, we found out that in subgroups of patients with G1, G2, G3, the mean values of this marker in the urine were 360.045.97 pg / ml, 361.926.89 pg / ml and 363.077.50 pg / ml, respectively. In patients with stage 3 T3N0M0 bladder cancer, the average level of TNF-β in the urine was 38.274.68 pg / ml, with this indicator in the control group being 33.824.62 pg / ml, but this difference did not was statistically significant (p> 0.05). In patients with bladder cancer and the degree of G1 neoplasia, the average level of TNF-β in the urine was 37.014.46 pg / ml, at the degree of G2 it was 38.304.49 pg / ml, and at the degree of neoplasia of the tumor G3 it equaled 40.014.83 pg / ml. Our study had the purpose to determine the molecular markers of VEGF, TNF-α and TNF-β in the urine of patients with bladder cancer stage T3N0M0 and establish their relationship with the degree of neoplasia G, and showed that the average level of VEGF in the urine was 245.657.90 pg / ml and significantly exceeded this indicator in the control group, which amounted to 131.237.80 pg / ml. However, this difference was statistically significant. In the diagnosis of bladder cancer, the sensitivity and specificity of urinary TNF-α levels were low and were 30% and 20%, respectively, and TNF-β levels they were even lower – 25% and 20%, respectively, which is not representative for the disease. Conclusion. Thus, the determination of the molecular markers of VEGF, TNF-α and TNF-β in the urine of patients with bladder cancer in stage T3N0M0 may serve the basis for the development of new methods for early diagnosis of the disease, as well as predicting the course and evaluating the effectiveness of treatment.

Keywords: bladder cancer, genotype, vascular endothelial growth factor, tumor necrosis factor, polymorphism, differentiation

Full text: PDF (Ukr) 213K

1. Rak v Ukraini, 2017-2018. Zakhvoryuvanist, smertnist, pokaznyky diyalnosti onkolohichnoi sluzhby [Cancer in Ukraine, 2017-2018. Morbidity, mortality, indicators of oncology service activity]. Byuleten Natsionalnoho kantser-reyestru Ukrainy. 2019; 20: 58-9. [Ukrainian]
2. Popkov VM, Ponukalyn AN, Zakharova NB. Faktor rosta endotelyya sosudov v dyahnostyke metastazov myshechno-ynvazyvnoho raka mochevoho puzyrya [Vascular endothelial growth factor in the diagnosis of metastases of muscle-invasive bladder cancer]. Onkourolohyya. 2016; 2(12): 53-7. [Russian] https://doi.org/10.17650/1726-9776-2016-12-2-53-57
3. Fu D, Li P, Cheng W, Tian F, Xu X, Yi X, et al. Impact of vascular endothelial growth factor gene-gene and gene-smoking interaction and haplotype combination on bladder cancer risk in Chinese population. Oncotarget. 2017 Apr 4; 8(14): 22927-35. https://www.ncbi.nlm.nih.gov/pubmed/28206971. https://www.ncbi.nlm.nih.gov/pmc/articles/5410274. https://doi.org/10.18632/oncotarget.15287
4. Song Y, Yang Y, Liu L, Liu X. Association between five polymorphisms in vascular endothelial growth factor gene and urinary bladder cancer risk: A systematic review and meta-analysis involving 6671 subjects. Gene. 2019 May 25; 698: 186-97. https://www.ncbi.nlm.nih.gov/pubmed/ 30849545. https://doi.org/10.1016/j.gene.2019.02.070
5. Wang J, Shen C, Fu Y, Yu T, Song J. The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis. Onco Targets Ther. 2017 Mar 21; 10: 1725-34. https://www.ncbi.nlm.nih.gov/pubmed/28356760. https://www.ncbi.nlm.nih.gov/pmc/articles/5367456. https://doi.org/10.2147/OTT.S125965
6. Stingl Jankovic K, Hudolin T, Kastelan Z, Zunec R, Grubic Z. The possible role of the tumour necrosis factor polymorphisms and human leucocyte antigens in the development of prostate cancer Int J Immunogenet. 2016 Jun; 43(3): 143-50. https://www.ncbi.nlm.nih.gov/pubmed/27102235. https://doi.org/10.1111/iji.12262
7. Song Y, Hu J, Chen Q, Guo J, Zou Y, Zhang W, et al. Association between vascular endothelial growth factor rs699947 polymorphism and the risk of three major urologic neoplasms (bladder cancer, prostate cancer, and renal cell carcinoma): A meta-analysis involving 11,204 subjects. Gene. 2018 Dec 30; 679: 241-52. https://www.ncbi.nlm.nih.gov/pubmed/30195633. https://doi.org/10.1016/j.gene.2018.09.005
8. Shen M, Zhou L, Zhou P, Zhou W, Lin X. Lymphotoxin β receptor activation promotes mRNA expression of RelA and pro-inflammatory cytokines TNFα and IL-1β in bladder cancer cells. Mol Med Rep. 2017 Jul; 16(1): 937-42. https://www.ncbi.nlm.nih.gov/pubmed/28586003. https://doi.org/10.3892/mmr.2017.6676
9. Hlants S. Mediko-biolohicheskaya statistika. Per s anhl. M: Praktika; 1998. 459 s. [Russian]