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Serum Interleukin and complement, levels in women with Ovarian Cancer

Lana Muhammad Ali, Parween Abdulsamad Ismail

Abstract


Background:

Ovarian cancer has a high mortality and delayed diagnosis. Inflammation is considered as a risk for ovarian carcinoma, and it contributes in all grades of tumor progression. Inflammation involved in the development of cancer cell and can be caused by   an increase in the formation of pro-inflammatory cytokines.

Objective: This research was conducted to assess serum Interleukin, complement levels C3 and C4 levels in ovarian cancer patients and to assess their impact in disease action.

Patients and methods.

The present study is composed of 85 women (mean age = 62.03±12.4 yrs) with clinically and pathologically confirmed ovarian cancer and 65 healthy women as a control group (mean age = 61±12.1 yrs). The measured biochemical parameters included: the level of serum Interleukins (IL-4, IL-6, IL-8) and complement levels  C3 and C4 .

Results: The results demonstrated significantly high values of serum Interleukin levels  (IL-4, IL-6, and IL-8) (   p<0.001, p<0.002, p<0.01) respectively and significantly high  values  (p < 0.01, p < 0.012) respectively in serum  complement levels  C3 and C4 in ovarian cancer in comparison with control group.

 Conclusion: An elevation of serum Interleukins levels, and complement levels C3 and C4 in cases of Ovarian carcinoma in our study is importance as a marker of the disease.

Keywords


Ovarian cancer, Interleukins, complement levels C3 and C4

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Abbritti RV, Polito F, Cucinotta M, Lo Giudice C, Caffo M, Tomasello C, et al.

Meningiomas and Proteomics: Focus on New Potential Biomarkers and Molecular

Pathways. Cancer Genomics Proteomics. 2016;13(5):369-79

Ajona D, Pajares MJ, Corrales L, Perez-Gracia JL, Agorreta J, Lozano MD, et al.

Investigation of complement activation product c4d as a diagnostic and prognostic

biomarker for lung cancer. J Natl Cancer Inst. 2013;105(18):1385-93.

Bandini S, Curcio C, Macagno M, Quaglino E, Arigoni M, Lanzardo S, et al. Early onset and enhanced growth of autochthonous mammary carcinomas in C3-deficient Her2/neu transgenic mice. Oncoimmunology. 2013;2(9):e26137.

Benoy IH, Salgado R, Van Dam P, et al. Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin Cancer Res 2004; 10: 7157–7162. DOI: 10.1158/1078-0432.CCR-04-0812.

Charbonneau B, Goode EL, Kalli KR, Knutson KL and Derycke MS: 2013.The immune system in the pathogenesis of ovarian cancer. Crit Rev Immunol 33: 137-164.

Chen LY, Fan J, Chen H, et al. The IL-8/ CXCR1 axis is associated with cancer stem cell-like properties and correlates with clinical prognosis in human pancreatic cancer cases. Sci Rep 2014; 4: 5911. DOI: 10.1038/srep05911.

Chen Y, Shi M, Yu GZ, et al. Interleukin-8, a promising predictor for prognosis of pancreatic cancer. World J Gastroenterol 2012; 18: 1123–1129. DOI: 10.3748/wjg. v18.i10.1123.

Cho MS, Vasquez HG, Rupaimoole R, Pradeep S, Wu S, Zand B, et al. Autocrine effects of tumor-derived complement. Cell Rep. 2014;6(6):1085-1095.

Chung L, Moore K, Phillips L, Boyle FM, Marsh DJ, Baxter RC. Novel serum protein biomarker panel revealed by mass spectrometry and its prognostic value in breast cancer. Breast Cancer Res. 2014;16(3):R63.

Crowther J. R.: ELISA. Theory and Practice. Methods Mol Bio 42, 1-223 (1995)

Dalal V, Kumar R, Kumar S, et al. Biomarker potential of IL-6 and VEGF-A in ascitic fluid of epithelial ovarian cancer patients. Clin Chim Acta 2018; 482: 27–32. DOI: 10.1016/j.cca.2018.03.019

Duan ZG and Yang WM: , 2005 .Analysis of cytokines (IL-2, IL-8, IL-10) in the expressed prostatic secretions of chronic prostatitis. Zhonghua Nan Ke Xue 11: 201-203.

Dubosq F, Ploussard G, Soliman H, Turpin E, Latil A, Desgrandchamps F, de The H and Mongiat-Artus P: Identification of a three-gene expression signature of early recurrence in non-muscle-invasive urothelial cell carcinoma of the bladder. Urol Oncol 30: 833-840, 2012.

Dvorak K, Dvorak B. Role of interleukin 6 in Barett’s esophagus pathogenesis. World of Gastroenterol 2013;19:2307 12

Ebrahimi B, Tucker SL, Li D, et al. Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis. Cancer 2004; 101: 2727–2736. DOI: 10.1002/cncr.20672.

Giuntoli RL 2nd, Webb TJ, Zoso A, Rogers O, Diaz-Montes TP, Bristow RE, Oelke M. 2009.

Hammody RH, , Mohammed Q A, Fareed AT. Serum immuinoglobulin and complement levels in patients with breast cancer Asian J Pharm Clin Res, Vol 11, Issue 6, 2018, 473-475.

Hecht JL, Kotsopoulos J, Hankinson SE and Tworoger SS: Relationship between epidemiologic risk factors and hormone receptor expression in ovarian cancer:

Hennessy BT, Coleman RL and Markman M: Ovarian cancer. Lancet 374: 1371-1382, 2009.

Imai M, Landen C, Ohta R, Cheung NK, Tomlinson S. Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer. Cancer Res. 2005;65(22):10562-8.

Jammal MP, Agrimaldo M , Thales P S, Eddie F CMurta and Rosekeila S N. Cytokines and Prognostic Factors in Epithelial Ovarian Cancer. Clinical Medicine Insights: Oncology 2016:10 :71–76 doi: 10.4137/CMO.S38333.

Jemal A, Siegel R, Ward E, et al:2009. Cancer statistics, 2009. CA Cancer J Clin.; 59: 225 –249.

Kallio J, Hamalainen M, Luukkaala T, et al. Resistin and interleukin 6 as predictive factors for recurrence and long-term prognosis in renal cell cancer. Urol Oncol 2017; 35: 544. e525–544. e531. DOI: 10.1016/j.urolonc.2017.05.005.

Kanmura S, Uto H, Sato Y, Kumagai K, Sasaki F, Moriuchi A, et al. The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma. J Gastroenterol. 2010;45(4):459-67.

Kawabata A, Yanaihara N, Nagata C, et al. Prognostic impact of interleukin-6 expression in stage I ovarian clear cell carcinoma. Gynecol Oncol 2017; 146: 609–614. DOI: 10.1016/j.ygyno.2017.06.027.

Kemper C, Atkinson JP, Hourcade DE. Properdin: emerging roles of a patternrecognition molecule. Annu Rev Immunol. 2010;28:131-55

Kolev M, Towner L, Donev R. Complement in cancer and cancer immunotherapy. Arch Immunol Ther Exp (Warsz). 2011;59(6):407-19.

Kwak JW, Laskowski J, Li HY, McSharry MV, Sippel TR, Bullock BL, et al. Complement Activation via a C3a Receptor Pathway Alters CD4(+) T Lymphocytes and Mediates Lung Cancer Progression. Cancer Res. 2018;78(1):143-156.

Luming Liu1, 2018. Serum levels of IL-6, IL-8, and IL-10 are indicators of prognosis in pancreatic cancer. Journal of International Medical Research 2018, Vol. 46(12) 5228–5236

Lippitz BE and Harris RA. Cytokine patterns in cancer patients: a review of the correlation between interleukin 6 and prognosis. Oncoimmunology 2016; 5: e1093722.

Lo MC, Yip TC, Ngan KC, et al. Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres. Cancer Letters 2013; 335: 81–92. DOI: 10.1016/j.canlet.2013.01.052.

Mamidi S, Hone S, Kirschfink M. The complement system in cancer: Ambivalence between tumour destruction and promotion. Immunobiology. 2017;222(1):45-54.

Mamidi S, Hone S, Kirschfink M. The complement system in cancer: Ambivalence between tumour destruction and promotion. Immunobiology. 2017;222(1):45-54.

Mehan MR, Ayers D, Thirstrup D, Xiong W, Ostroff RM, Brody EN, et al. Protein signature of lung cancer tissues. PLoS One. 2012;7(4):e35157.

Mendez, Morales-Vasquez, Gómora MJ, Calvillo-Robledo, Lopez-Basave and Pedernera. 2016. Sexual Steroids in Epithelial Ovarian Cancer. Ovarian Cancer

Meningiomas and Proteomics: Focus on New Potential Biomarkers and Molecular

Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement System Part I - Molecular Mechanisms of Activation and Regulation. Front Immunol. 2015;6:262.

Merritt WM, Lin YG, Spannuth WA, Fletcher MS, Kamat AA, Han LY, Landen CN, Jennings N, De Geest K, Langley RR, Villares G, Sanguino A, Lutgendorf SK, Lopez-Berestein G, Bar-Eli MM, Sood AK. 2008 Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst. 5;100(5):359-72.

Mollnes, T. E. 1997. Analysis of in vivo complement activation, p. 78.1-78.8. In L. A. Herzenberg, D. M. Weir, L. A. Herzenberg, and C. Blackwell (ed.), Weir's handbook of experimental immunology, 5th ed. Blackwell Science, Boston, Mass.

Moser M, Murphy KM. 2000.Dendritic cell regulation of TH1-TH2 development. Nat Immunol.;1(3):199–205

Ning Y and Lenz HJ. Targeting IL-8 in colorectal cancer. Expert Opin Ther Targets 2012; 16: 491–497. DOI: 10.1517/ 14728222.2012.677440.

Pio R, Corrales L, Lambris JD. The role of complement in tumor growth. Adv Exp Med Biol. 2014;772:229-62.

Piura B, Medina L, Rabinovich A, Dyomin V, Huleihel M. Thalidomide distinctly affected TNF-α, IL-6 and MMP secretion by an ovarian cancer cell line (SKOV-3) and primary ovarian cancer cells. Eur Cytokine Netw 2013 Jul-Sep;24(3):122-9.

Redford PS, Murray PJ and O'Garra A: 2011.The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol 4: 261-270.

results from the Nurses' Health Study. Cancer Epidemiol Biomarkers Prev 18: 1624-1630, 2009.

Ricklin D, Mastellos DC, Reis ES, Lambris JD. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018; 14(1):26-47.

Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nat Rev Nephrol. 2016;12(7):383-401.

Russo RC, Garcia CC, Teixeira MM, et al. The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases. Expert Rev Clin Immunol 2014; 10: 593–619. DOI: 10.1586/1744666X.2014.894886.

Sanmamed MF, Carranza-Rua O, Alfaro C, et al. Serum Interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins. Clin Cancer Res 2014; 20: 5697–5707.

Sapochnik M, Haedo MR, Fuertes M, et al. Autocrine IL-6 mediates pituitary tumor senescence. Oncotarget 2017; 8: 4690–4702. DOI: 10.18632/oncotarget.13577.

Schmidt CQ, Lambris JD, Ricklin D. Protection of host cells by complement regulators. Immunol Rev. 2016;274(1):152-171.

Takeda K, Fujii N, Nitta Y,SakiharaH, Nakayama K, Rikiishi H, et al. Murine tumor cells metastasizing selectively in the liver: Ability to produce hepatocyte-activating cytokines interleukin-I and/or -6. Jpn J CancerRes 1991;82:1299-1308.

Tao S, Haug U, Kuhn K, Brenner H. Comparison and combination of blood-based inflammatory markers with faecal occult blood tests for non-invasive colorectal cancer screening. Br J Cancer. 2012;106(8):1424-30.

Tchirkov A, Khalil T, Chautard E, et al. Interleukin-6 gene amplification and shortened survival in glioblastoma patients. Br J Cancer 2007; 96: 474–476. DOI: 10.1038/ sj.bjc.6603586.

Verma G, Bhatia H and Datta M. Gene expression profiling and pathway analysis identify the integrin signaling pathway to be altered by IL-1 beta in human pancreatic cancer cells: role of JNK. Cancer Lett 2012; 320: 86–95.

Wang H, Luo C, Zhu S, Fang H, Gao Q, Ge S, et al. Serum peptidome profiling for the diagnosis of colorectal cancer: discovery and validation in two independent cohorts. Oncotarget. 2017;8(35):59376-59386.

Wang J, Luo F, Lu JJ, Chen PK, Liu P and Zheng W: VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors. Int J Cancer 97: 163-167, 2002.

Wang Y, Xu RC, Zhang XL, Niu XL, Qu Y, Li LZ, Meng XY. Interleukin-8 secretion by ovarian cancer cells increases anchorage-independent growth, proliferation, angiogenic potential, adhesion and invasion. Cytokine. 2012 Jul;59(1):145-55.

Zhang Z, Jia L, Feng Y and Zheng W: Overexpression of folliclestimulating hormone receptor facilitates the development of ovarian epithelial cancer. Cancer Lett 278: 56-64, 2009.

Zhao BB, Yang ZJ, Wang Q, Pan ZM, Zhang W and Li L: Clinical validation of multiple biomarkers suspension array technology for ovarian cancer. Zhonghua Fu Chan Ke Za Zhi. 52:11–19. 2017.

Zhao P, Wu J, Lu F, Peng X, Liu C, Zhou N, et al. The imbalance in the complement system and its possible physiological mechanisms in patients with lung cancer. BMC Cancer. 2019;19(1):201


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