Local cytokine concentration in patients with non-muscle invasive bladder cancer of low malignant potential and with varying rates of recurrence
- Authors: Belyakova L.I1, Shevchenko A.N.1, Shulgina O.G.1, Sagakyant A.B.1, Burtsev D.V.2, Zlatnik E.Y.1, Novikova I.A.1, Filatova E.V.1, Khvan V.K.1, Khomutenko I.A.1
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Affiliations:
- National Medical Research Center of Oncology, Ministry of Health of Russia
- Regional Consultative and Diagnostic Center
- Issue: Vol 18, No 4 (2022)
- Pages: 63-71
- Section: DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
- Published: 03.12.2022
- URL: https://oncourology.abvpress.ru/oncur/article/view/1589
- DOI: https://doi.org/10.17650/1726-9776-2022-18-4-63-71
- ID: 1589
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Full Text
Abstract
Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence.
Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).
Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.
Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.
About the authors
L. I Belyakova
National Medical Research Center of Oncology, Ministry of Health of Russia
Author for correspondence.
Email: drlbelyakova@yandex.ru
ORCID iD: 0000-0001-7955-3473
SPIN-code: 3382-8559
Lyubov’ Igorevna Belyakova
63 14th Liniya, Rostov-on-Don 344037
Russian Federation
A. N. Shevchenko
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-9468-134X
63 14th Liniya, Rostov-on-Don 344037
Russian FederationO. G. Shulgina
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0001-6828-145X
63 14th Liniya, Rostov-on-Don 344037
Russian FederationA. B. Sagakyant
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0003-0874-5261
63 14th Liniya, Rostov-on-Don 344037
Russian FederationD. V. Burtsev
Regional Consultative and Diagnostic Center
127 Pushkinskaya St., Rostov-on-Don 344000
Russian FederationE. Yu. Zlatnik
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-1410-122X
63 14th Liniya, Rostov-on-Don 344037
Russian FederationI. A. Novikova
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-6496-9641
63 14th Liniya, Rostov-on-Don 344037
Russian FederationE. V. Filatova
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-7904-4414
63 14th Liniya, Rostov-on-Don 344037
Russian FederationV. K. Khvan
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-0036-7190
63 14th Liniya, Rostov-on-Don 344037
Russian FederationI. A. Khomutenko
National Medical Research Center of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0003-0003-8044
63 14th Liniya, Rostov-on-Don 344037
Russian FederationReferences
- Kit O.I., Franciyanc E.M., Dimiriadi S.N. et al. Neoangiogenesis and fibrinolytic system biomarkers expression in the dynamics of experimental kidney ischemia in rats. Eksperimental’naya i klinicheskaya urologiya = Experimental and Clinical Urology 2015;(1):20–3. (In Russ.).
- State of oncological care in Russia in 2020. Eds.: А.D. Kaprin, V.V. Starinskiy, A.O. Shachzadova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2021. 239 p. (In Russ.).
- Belyakova L.I., Shevchenko A.N., Sagakyants A.B., Filatova E.V. Markers of bladder cancer: their role and prognostic significance (literature review). Onkourologiya = Cancer Urology 2021;17(2):145–56. (In Russ.). doi: 10.17650/1726-9776-2021-17-2-145-156
- The European Association of Urology (EAU) Urolithiasis Guidelines. Presented at the EAU Annual Congress Amsterdam 2020. EAU Guidelines Office, Arnhem, The Netherlands. Available at: http://uroweb.org/guidelines/compilations-of-all-guidelines/.
- Malignant tumors in Russia in 2020 (morbidity and mortality). Eds.: А.D. Kaprin, V.V. Starinskiy, A.O. Shachzadova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2021. 252 p. (In Russ.).
- Adeishvili G.Z. Evaluation of diagnostic and prognostic value of cytokeratins in patients with bladder cancer. Dis. … candidate of medical sciences. Saint Petersburg, 2017. 13 p. (In Russ.).
- Kovylina M.V., Prilepskaya E.A., Tupikina N.V. et al. Grading of urothelial carcinoma of the bladder. Onkourologiya = Cancer Urology 2017;13(2):87–95. doi: 10.17650/1726-9776-2017-13-2-87-95
- Belyakova L.I., Shevchenko A.N., Sagakyants A.B. et al. The number of cancer stem cells in the tumor tissue and perifocal tissue of non-muscle invasive bladder cancer. Yuzhno-Rossiyskiy onkologicheskij zhurnal = South Russian Journal of Cancer 2021;3(1):6–14. (In Russ.). doi: 10.37748/2686-9039-2022-3-1-1
- Gliakin D.S., Samoylova A.V., Gunin A.G. Proinflammatory cytokines in patients with endometrial cancer. Problemy reproduktsii = Russian Journal of Human Reproduction 2012;(1):35–7. (In Russ.).
- Mashkina E.V., Kovalenko K.A., Fomina N.V., Shkurat T.P. Study of the association of polymorphic variants of cytokine genes with early embryonic losses. Ekologicheskaya genetika = Ecological Genetics 2014;12(1):19–27. (In Russ.). doi: 10.17816/ecogen12119-27
- Wang X., Ni S., Chen Q. et al. Bladder cancer cells induce immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through interleukin 10. Cell Biol Int 2017;41(2):177–86. doi: 10.1002/cbin.10716
- Blinnikov A.A., Ryazantsev E.V. The dynamics of some cytokines of plasma in the structure of surgical treatment of urinary bladder cancer. Vestnik Rossiyskogo Universiteta Druzhby Narodov. Seriya: Meditsina = RUDN Journal of Medicine 2008;(8):280–4. (In Russ.).
- Schafer Z.T., Brugge J.S. IL-6 involvement in epithelial cancers. J Clin Invest 2007;117(12):3660–3. doi: 10.1172/JCI34237
- Zaborskiy I.N., Ivanov S.A., Mushkarina T.Yu. et al. Study of association between molecular marker expression on tumor and immunocompetent cells and sensitivity to adjuvant and neoadjuvant therapy of bladder cancer. Onkourologiya = Cancer Urology 2019;15(2):100–6. (In Russ.). doi: 10.17650/1726-9776-2019-15-2-100-106
- Kit O.I., Ignatov S.N., Zlatnik E.Yu. et al. Role of cytokines in the formation of immunological microenvironment in low-grade brain gliomas, their significance for diagnosis and immunotherapy. Meditsinskiy vestnik Severnogo Kavkaza = Medical News of the North Caucasus 2021;16(4):433–8. (In Russ.). doi: 10.14300/mnnc.2021.16106
- Kadagidze Z.G., Chertkova A.I. Immunity and cancer. Prakticheskaya onkologiya = Practical Oncology 2016;17(2):62–73. (In Russ.).
- Zlatnik E.Yu., Ignatov S.N., Sagakyants A.B. et al. Predictive role of local cytokine levels in the course of poorly differentiated glial tumors. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education 2021;2. (In Russ.). doi: 10.17513/spno.30645
- Demidov L.V., Harkevich G.Yu., Timofeev I.V. Successes and failures of the use of cytokines in the drug therapy of some solid tumors. Prakticheskaya onkologiya = Practical Oncology 2003;4(3):140–7. (In Russ.).
- Shadpour P., Zamani M., Aghaalikhani N., Rashtchizadeh N. Inflammatory cytokines in bladder cancer. J Cell Physiol 2019. doi: 10.1002/jcp.28252
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