Evaluation of neutrophil granulocyte respiratory burst in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women. The ambiguity of neutrophils in the implementation of the immune response indicates their transformation into protumor cells in the late stages of the disease. In this regard, the aim of the study was to study the respiratory burst of neutrophilic granulocytes (NG) in the blood of patients with CRC at different stages of the disease and in the dynamics of treatment. The study included 99 patients with CRC in different stages and 112 practically healthy volunteers. The respiratory burst of neutrophils was assessed using chemiluminescent analysis of neutrophil granulocyte activity for 90 minutes on a 36-channel chemiluminescent analyzer “CL3607” (Russia). Statistical data processing was performed using Statistica 10 software packages (StatSoft Inc, USA). Statistical significance of differences was determined using the Mann–Whitney criterion equal to p < 0.05. In patients with CRC, an increase in the intensity of chemiluminescence (CL) and total synthesis of reactive oxygen species (ROS) was recorded both in a state of relative rest and under additional functional load, reflecting the state of the respiratory burst in patients’ neutrophils, both on the 1^st day of admission and on the 7^th day after surgery. The activation index is increased in patients with CRC at all stages and throughout the examination. Significant deviations in the indices of chemiluminescent activity of neutrophil granulocytes were recorded in patients with CRC: before surgery, an increase in the intensity of spontaneous CL was detected at stages II-IV of the disease, and induced CL at all stages, with the luminescence intensity at the late stage being higher. After surgical treatment, the spontaneous intensity of ROS production at stages I-III normalized, in the induced test, NG patients were still more reactive than the controls. The total ROS production by NG patients with CRC at all stages exceeded the indices of practically healthy people in the spontaneous and induced CL test both upon admission to the hospital and after treatment. The existing reserve capacity for ROS synthesis is also indicated by the increased neutrophil granulocyte activation index in all groups.

1. Vinnik Yu.S., Savchenko A.A., Peryanova O.V., Teplyakova O.V., Yakimov S.V., Teplyakova E.Yu., Meshkova O.S. Clinical aspects of the use of chemiluminescent analysis. Sibirskoye meditsinskoye obozreniye = Siberian Medical Review, 2006, no. 3, pp. 3-6. (In Russ.)

2. Garmanova T.N., Bredikhin M.I., Tulina I.A., Tsarkov P.V. The role of inflammation in the course and treatment of colorectal cancer. Research’n Practical Medicine Journal = Research’n Practical Medicine Journal, 2018, Vol. 5, no. 4, pp. 36-45. (In Russ.)

3. Gitelzon I.I., Sandalova T.P. Prospects for the application of bioluminescent methods in medicine. Vrachebnoye delo = Medical Practicе, 1990, no. 9, p. 31. (In Russ.)

4. Dorokhina N.A., Savchenko A.A., Chesnokov A.B., Polonskaya Zh.G., Olkhovsky I.A., Shakina N.A. Use of specific antigen preparations as inducers of respiratory burst of blood leukocytes in chemiluminescent analysis. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics, 2001, no. 1, pp. 39-43. (In Russ.)

5. Efremenko E.N., Ugarova N.N., Lomakina G.Yu., Senko O.V., Stepanov N.A., Maslova O.V., Aslanly A.G., Lyagin I.V. Bioluminescent ATP-metry: practical aspects. Moscow: Nauchnaya biblioteka, 2022. 376 p.

6. Zholmurzaeva R.S. Organizational foundations of colorectal cancer screening in global medical practice. Literature review. Nauka i zdravookhraneniye = Science and Healthcare, 2019, no. 2, pp. 13-24. (In Russ.)

7. Kit O.I., Shaposhnikov A.V., Zlatnik E.Yu., Nikipelova E.A., Zakora G.I., Gevorkyan Yu.A., Averkin M.A., Shulikov P.B. Tissue level of cytokines in colorectal cancer. Tyumenskiy meditsinskiy zhurnal = Tyumen Medical Journal, 2011, no. 3-4, pp. 21-22. (In Russ.)

8. Maltseva V.N., Safronova V.G. Ambiguity of the role of neutrophil in tumor genesis. Tsitologiya = Tsitologiya, 2009, Vol. 51, no. 6, pp. 467-474. (In Russ.)

9. Nesterova I.V., Kovaleva S.V., Chudilova G.A., Lomtatidze L.V., Evglevsky A.A. Dual role of neutrophilic granulocytes in the implementation of antitumor protection. Immunologiya = Immunologiya, 2012, no. 5, pp. 281-285. (In Russ.)

10. Nikipelova E.A., Kit O.I., Shaposhnikov A.V., Zlatnik E.Yu., Novikova I.A. Colocarcinogenesis: oncoimmunology of local changes. Zlokachestvennyye opukholi = Malignant Tumors, 2016, no. 4S1, pp. 81-86. (In Russ.)

11. Balkwill F., Mantovani A. Inflammation and cancer: back to Virchow? Lancet, 2001, Vol. 357, no. 9255, pp. 539-545.

12. Bekes E.M., Schweighoter B., Kupriyanova T.A ., Zajac, E., Ardi V.C., Quigley J.P., Deryugina E.I. Tumor-Recruited Neutrophils and Neutropil TIMP-free MMP-9 Regulate Coordinately the Levels of Tumor Angiogenesis and Efficiency of Malignant cell Intravasation. Am. J. Pathol., 2011, Vol. 179, no. 3, pp. 1455-1470.

13. Fridlender Z.G., Sun J., Kim S., Kapoor V., Cheng G., Ling L., Worthen G.S., Albelda S.M. Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell, 2009, Vol. 16, no. 3, pp. 183-194.

14. Galdiero M.R., Garlanda C., Jaillon S., Marone G., Mantovani A. Tumor associated macrophages neutrophils in tumor progression. J. Cell. Physiol., 2013, Vol. 228, no. 7, pp. 1404-1412.

15. Khazaie K., Blatner N.R., Khan M.W., Gounari F., Gounaris E., Dennis K., Bonertz A., Tsai Fu-N., Strouch M.J., Cheon E., Phillips J.D., Beckhove P., Bentrem D.J. The significant role of mast cells in cancer. Cancer Metastasis Rev., 2011, Vol. 30, no. 1, pp. 45-60.

16. Knaapen A.M., Güngör N., Schins R.P., Borm P.J., Van Schooten F.J. Neutropihis and respiratory tract DNA damage and mutagenesis: а review. Mutagenesis, 2006, Vol. 21, no. 4, pp. 225-236.

17. Ouakrim D.A., Pizot C., Boniol M., Malvezzi M., Boniol M., Negri E., Bota M., Jenkins M.A., Bleiberg H., Autier P. Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ, 2015, Vol. 351, h4970. doi: 10.1136/bmj.h4970

18. Shen M., Hu P., Donskov F., Wang G., Liu Q., Du J. Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Rewiewand Meta-Analysis. Plos One, 2014, Vol. 9, no. 6, e98259. doi: 10.1371/journal.pone.0098259.

19. Terzic J., Grivennikov S., Karin E., Karin M. Inflammation and colon cancer. Gastroenterology, 2010, Vol. 138, no. 6, pp. 2101-2114.e5.