Haemocytometric profile and plasma levels of selected cytokines in patients at various stages of cervical cancer
DOI:
https://doi.org/10.15584/ejcem.2023.4.2Keywords:
cancer stage, cervical cancer, haemocytometry, interleukin-6, parityAbstract
Introduction and aim. Reports have shown that there is alteration in haematological and inflammatory processes in patients with cervical cancer. However, there is the dearth of information on the pattern of alteration in Nigerian patients with cervical cancer at various stages of the disease. Therefore, haemocytometric profile and plasma levels of interleukin-6 (IL-6) and IL-12 were determined in Nigerian patients with cervical cancer at various stages of the disease.
Material and methods. Eighty-nine adults consisting of 49 patients with cervical cancer and 40 apparently healthy controls were enrolled into this study. Haemocytometric profile was determined using automated haematology analyzer while the plasma levels of interleukin-6 (IL-6) and IL-12 were determined using ELISA.
Results. Of the participants with cervical cancer, 6.12%, 24.49%, 53.06% and 16.33% were in stages I, II, III and IV respectively. The mean plasma IL-6 level was significantly higher in patients at stage IV of the cancer compared with those in stages I, II and III. No significant differences were observed in the mean plasma IL-12 level, and the haemocytometric profile when patients in different stages of the cancer were compared with one another. Plasma IL-6 had significant positive correlation with the lymphocytes count and cancer stage but had significant negative correlation with packed cell volume (PCV), haemoglobin and total white blood cells count (WBC) in patients with cervical cancer.
Conclusion. Interleukin-6 appears to play an important role in the progression of cervical cancer and could be involved in cervical cancer-associated alteration in haemocytometric profile.
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References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492
World Health Organization. Cervical cancer. Fact sheet: World Health Organization; 2022.
Song B, Ding C, Chen W, Sun H, Zhang M, Chen W. Incidence and mortality of cervical cancer in China, 2013. Chin J Cancer Res. 2017;29(6):471-476. doi: 10.21147/j.issn.1000-9604.2017.06.01
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi: 10.3322/caac.21660
IARC/ICO Information Centre on HPV and Cancer. Human Papilloma Virus and Related Cancers, Fact Sheet 2017. 2017.
Ilevbare OE, Adegoke AA, Adelowo CM. Drivers of cervical cancer screening uptake in Ibadan, Nigeria. Heliyon. 2020;6(3):e03505. doi: 10.1016/j.heliyon.2020.e03505
de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141(4):664-670. doi: 10.1002/ijc.30716
Hamad NJ. Hematological changes associated with the carcinoma of the uterine cervix. J Univ Babylon. 2005;10(4):1-5.
Tavares-Murta BM, Mendonça MA, Duarte NL, et al. Systemic leukocyte alterations are associated with invasive uterine cervical cancer. Int J Gynecol Cancer. 2010;20(7):1154-1159. doi: 10.1111/igc.0b013e3181ef8deb
Nath A, Kumar R, Trivedi V, et al. MDA elevation and haematological derangements at first clinical presentation in cervical cancer patients. Int J Pharm Sci Rev Res. 2015;30:175-179.
Kose M, Celik F, Kose SK, Arioz DT, Yilmazer M. Could the platelet-to-lymphocyte ratio be a novel marker for predicting invasiveness of cervical pathologies? Asian Pac J Cancer Prev. 2015;16(3):923-926. doi: 10.7314/apjcp.2015.16.3.923
García Paz F, Madrid Marina V, Morales Ortega A, et al. The relationship between the antitumor effect of the IL-12 gene therapy and the expression of Th1 cytokines in an HPV16-positive murine tumor model. Mediators Inflamm. 2014;2014:510846. doi: 10.1155/2014/510846
Murooka TT, Ward SE, Fish EN. Chemokines and cancer. Cancer Treat Res. 2005;126:15-44. doi: 10.1007/0-387-24361-5_2
Heikkilä K, Ebrahim S, Lawlor DA. Systematic review of the association between circulating interleukin-6 (IL-6) and cancer. Eur J Cancer. 2008;44(7):937-945. doi: 10.1016/j.ejca.2008.02.047
Zarogoulidis P, Yarmus L, Darwiche K, et al. Interleukin-6 cytokine: a multifunctional glycoprotein for cancer. Immunome Res. 2013;9(62):16535. doi: 10.1186/2090-5009-9-1.
Tjiong MY, van der Vange N, ten Kate FJ, et al. Increased IL-6 and IL-8 levels in cervicovaginal secretions of patients with cervical cancer. Gynec Oncol. 1999;73(2):285-291. doi: 10.1006/gyno.1999.5358
Tavares-Murta BM, de Resende AD, Cunha FQ, Murta EF. Local profile of cytokines and nitric oxide in patients with bacterial vaginosis and cervical intraepithelial neoplasia. Eur J Obstet Gynecol Reprod Biol. 2008;138(1):93-99. doi: 10.1016/j.ejogrb.2007.06.015
Bustamam A, Ibrahim S, Devi N, Halkim MN, Al-Zubairi AS, Syam M. The establishment and use of an in vivo animal model for cervical intra-epithelial neoplasia. Int J Cancer Res. 2008;4(3):61-70.
Nguyen KG, Vrabel MR, Mantooth SM, et al. Localized Interleukin-12 for Cancer Immunotherapy. Front Immunol. 2020;11:575597. doi: 10.3389/fimmu.2020.575597
e Habiba U, Rafiq M, Khawar MB, Nazir B, Haider G, Nazir N. The multifaceted role of IL-12 in cancer. Advances in Cancer Biology-Metastasis. 2022;5:100053. doi.org/10.1016/j.adcanc.2022.100053
Brunda MJ, Luistro L, Warrier RR, et al. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med. 1993;178(4):1223-1230. doi: 10.1084/jem.178.4.1223
Smyth MJ, Taniguchi M, Street SE. The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol. 2000;165(5):2665-2670. doi: 10.4049/jimmunol.165.5.2665
Bashyam H. Interleukin-12: a master regulator. J Exp Med. 2007;204(5):969. doi: 10.1084/jem.2045fta
Zaharoff DA, Hance KW, Rogers CJ, Schlom J, Greiner JW. Intratumoral immunotherapy of established solid tumors with chitosan/IL-12. J Immunother 2010;33(7):697-705. doi: 10.1097/CJI.0b013e3181eb826d
Steding CE, Wu ST, Zhang Y, Jeng MH, Elzey BD, Kao C. The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis. Immunology. 2011;133(2):221-238. doi: 10.1111/j.1365-2567.2011.03429.x
Saiki I, Sato K, Yoo YC, et al. Inhibition of tumor-induced angiogenesis by the administration of recombinant interferon-gamma followed by a synthetic lipid-A subunit analogue (GLA-60). Int J Cancer. 1992;51(4):641-645. doi: 10.1002/ijc.2910510422
Buszello H. Antiproliferative effects of four different cytokines on renal carcinoma cell lines. Anticancer Res. 1995;15(3):735-738.
Voest EE, Kenyon BM, O'Reilly MS, Truitt G, D'Amato RJ, Folkman J. Inhibition of angiogenesis in vivo by interleukin 12. J Natl Cancer Inst. 1995;87(8):581-586. doi: 10.1093/jnci/87.8.581
Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749-795. doi: 10.1146/annurev.immunol.15.1.749
Wall L, Burke F, Barton C, Smyth J, Balkwill F. IFN-gamma induces apoptosis in ovarian cancer cells in vivo and in vitro. Clin Cancer Res. 2003;9(7):2487-2496.
Atkins MB, Robertson MJ, Gordon M, et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res. 1997;3(3):409-417.
Noguchi Y, Jungbluth A, Richards EC, Old LJ. Effect of interleukin 12 on tumor induction by 3-methylcholanthrene. Proc Natl Acad Sci USA. 1996;93(21):11798-11801. doi: 10.1073/pnas.93.21.11798
Bajetta E, Del Vecchio M, Mortarini R, et al. Pilot study of subcutaneous recombinant human interleukin 12 in metastatic melanoma. Clin Cancer Res. 1998;4(1):75-85.
Colombo MP, Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev. 2002;13(2):155-168. doi: 10.1016/s1359-6101(01)00032-6
Wadler S, Levy D, Frederickson HL, et al. A phase II trial of interleukin-12 in patients with advanced cervical cancer: clinical and immunologic correlates. Eastern Cooperative Oncology Group study E1E96. Gynecol Oncol. 2004;92(3):957-964. doi: 10.1016/j.ygyno.2003.12.022
Candelaria M, Cetina L, Dueñas-González A. Anemia in cervical cancer patients: implications for iron supplementation therapy. Med Oncol. 2005;22(2):161-168. doi: 10.1385/MO:22:2:161
Grogan M, Thomas GM, Melamed I, et al. The importance of hemoglobin levels during radiotherapy for carcinoma of the cervix. Cancer. 1999;86(8):1528-1536. doi: 10.1002/(sici)1097-0142(19991015)86:8<1528::aid-cncr20>3.0.co;2-e
Fyles AW, Milosevic M, Pintilie M, Syed A, Hill RP. Anemia, hypoxia and transfusion in patients with cervix cancer: a review. Radiother Oncol. 2000;57(1):13-19. doi: 10.1016/s0167-8140(00)00245-0
Serkies K, Badzio A, Jassem J. Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy. Acta Oncol. 2006;45(6):695-701. doi: 10.1080/02841860600833160
Shen WJ, Fu S, Li N, et al. Decreased Mean Platelet Volume is Associated with Cervical Cancer Development. Asian Pac J Cancer Prev. 2017;18(7):1769-1772. doi: 10.22034/APJCP.2017.18.7.1769
Wang L, Jia J, Lin L, et al. Predictive value of hematological markers of systemic inflammation for managing cervical cancer. Oncotarget. 2017;8(27):44824-44832. doi: 10.18632/oncotarget.14827
Ahmed Y, Okwesili A, Malami I, et al. Some Haematological and Haemostatic Parameters Among Women with Cervical Cancer in Sokoto, North Western Nigeria. Sokoto J Med Lab Sci. 2017;2(1):236-251.
Granger JM, Kontoyiannis DP. Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study. Cancer. 2009;115(17):3919-3923. doi: 10.1002/cncr.24480
Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost. 2011;9(2):237-249. doi: 10.1111/j.1538-7836.2010.04131.x
Goubran HA, Stakiw J, Radosevic M, Burnouf T. Platelet-cancer interactions. Semin Thromb Hemost. 2014;40(3):296-305. doi: 10.1055/s-0034-1370767
Seretis C, Youssef H, Chapman M. Hypercoagulation in colorectal cancer: what can platelet indices tell us? Platelets. 2015;26(2):114-118. doi: 10.3109/09537104.2014.894969
Paradkar PH, Joshi JV, Mertia PN, Agashe SV, Vaidya RA. Role of cytokines in genesis, progression and prognosis of cervical cancer. Asian Pac J Cancer Prev. 2014;15(9):3851-3864. doi: 10.7314/apjcp.2014.15.9.3851
Grivennikov S, Karin E, Terzic J, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell. 2009;15(2):103-113. doi: 10.1016/j.ccr.2009.01.001
Gyamfi J, Lee Y-H, Eom M, Choi J. Interleukin-6/STAT3 signalling regulates adipocyte induced epithelial-mesenchymal transition in breast cancer cells. Sci Rep. 2018;8(1):1-13. doi: 10.1038/s41598-018-27184-9
Jones SA, Jenkins BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol. 2018;18(12):773-789. doi: 10.1038/s41577-018-0066-7
Nguyen HH, Broker TR, Chow LT, et al. Immune responses to human papillomavirus in genital tract of women with cervical cancer. Gynecol Oncol. 2005;96(2):452-461. doi: 10.1016/j.ygyno.2004.10.019
Li B, Zhang L, Zhao J, et al. The value of cytokine levels in triage and risk prediction for women with persistent high-risk human papilloma virus infection of the cervix. Infect Agent Cancer. 2019;14:16. doi: 10.1186/s13027-019-0231-z
Hurst SM, Wilkinson TS, McLoughlin RM, et al. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity. 2001;14(6):705-714. doi: 10.1016/s1074-7613(01)00151-0
Marin V, Montero-Julian FA, Grès S, et al. The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin. J Immunol. 2001;167(6):3435-3442. doi: 10.4049/jimmunol.167.6.3435
Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003;24(1):25-29. doi: 10.1016/s1471-4906(02)00013-3
Afford SC, Pongracz J, Stockley RA, Crocker J, Burnett D. The induction by human interleukin-6 of apoptosis in the promonocytic cell line U937 and human neutrophils. J Biol Chem. 1992;267(30):21612-21616
Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006;25(3):315-322. doi: 10.1007/s10555-006-9001-7
Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ. CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem. 2009;284(49):34342-34354. doi: 10.1074/jbc.M109.042671
Wei LH, Kuo ML, Chen CA, et al. Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway. Oncogene. 2003;22(10):1517-1527. doi: 10.1038/sj.onc.1206226
Song Z, Lin Y, Ye X, et al. Expression of IL-1α and IL-6 is Associated with Progression and Prognosis of Human Cervical Cancer. Med Sci Monit. 2016;22:4475-4481. doi: 10.12659/msm.898569
Akchurin O, Patino E, Dalal V, et al. Interleukin-6 Contributes to the Development of Anemia in Juvenile CKD. Kidney Int Rep. 2019;4(3):470-483. doi: 10.1016/j.ekir.2018.12.006
Kim DK, Oh SY, Kwon HC, et al. Clinical significances of preoperative serum interleukin-6 and C-reactive protein level in operable gastric cancer. BMC Cancer. 2009;9:155. doi: 10.1186/1471-2407-9-155
Hidayat F, Labeda I, Sampetoding S, et al. Correlation of interleukin-6 and C-reactive protein levels in plasma with the stage and differentiation of colorectal cancer: A cross-sectional study in East Indonesia. Ann Med Surg (Lond). 2021;62:334-340. doi: 10.1016/j.amsu.2021.01.013
Tekalegn Y, Sahiledengle B, Woldeyohannes D, et al. High parity is associated with increased risk of cervical cancer: Systematic review and meta-analysis of case–control studies. Womens Health (Lond). 2022;18:17455065221075904. doi: 10.1177/17455065221075904
Castellsagué X, Muñoz N. Chapter 3: Cofactors in human papillomavirus carcinogenesis-role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr. 2003(31):20-28.
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