Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 3, May-June, p. 421–426

doi: 10.17219/acem/62120

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

IL-6, IL-8 and TNF-α levels correlate with disease stage in breast cancer patients

Yunfeng Ma1,A,B,C,D,E,F, Yi Ren2,A,B,C, Zhi-Jun Dai3,A,B,C, Cai-Jun Wu1,B,C, Yan-Hong Ji1,E, Jiru Xu1,A,B,C,E,F

1 Department of Pathogenic Microbiology and Immunology, Xi’an Jiaotong University Health Science Center, Xi’an, China

2 Department of Breast and Thyroid Surgery, Huai’an First People’s Hospital, Huai’an, China

3 Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Abstract

Background. Breast cancer is the most common cancer in Chinese women. Inflammation contributes to tumor progression and can be induced by excessive production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). However, how their levels relate to the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) by the tumor has not been investigated.
Objectives. The aim of the study is to more fully understand the significance of serum IL-6, IL-8 and TNF-α in breast cancers with different ER, PR and HER2 status.
Material and Methods. Preoperative serum samples were collected from 110 patients diagnosed with ductal carcinoma and 30 healthy control subjects. IL-6, IL-8 and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA). Associations of cytokine levels with clinical tumor stage were evaluated, and correlations of serum cytokine levels with ER, PR and HER2 expression were determined using the Pearson correlation coefficient.
Results. Serum levels of IL-6 and IL-8 were significantly higher in the subjects with ductal carcinoma than in the controls, and strongly correlated with clinical tumor stage, lymph node metastasis, and ER and HER2 antigen expression (p < 0.05). TNF-α levels in stage III carcinoma patients were significantly higher than in the controls (p < 0.01) and were associated with lymph node metastasis (p < 0.01). A strong positive correlation was found between IL-8 and TNF-α levels in the cancer patients (p < 0.0001).
Conclusion. The study showed that IL-6, IL-8 and TNF-α levels correlated with clinical disease stage and lymph node metastasis as well as with ER and HER2 antigen expression. Specifically, IL-6 and IL-8 seem to have significant potential as prognostic cancer biomarkers. Analyzing serum cytokine levels might help identify patients with a poor prognosis who may benefit from more aggressive disease management.

Key words

breast cancer, biomarkers, interleukin-6, TNF-α, interleukin-8

References (30)

  1. Cheung YT, Ng T, Shwe M, Ho HK, et al. Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: A multi-centered, prospective, cohort studydagger. Ann Oncol. 2015;26:1446–1451.
  2. Chin AR, Wang SE. Cytokines driving breast cancer stemness. Mol Cell Endocrinol. 2014;382:598–602.
  3. Jiang X, Shapiro DJ. The immune system and inflammation in breast cancer. Mol Cell Endocrinol. 2014;382:673–682.
  4. Esquivel-Velazquez M, Ostoa-Saloma P, Palacios-Arreola MI, Nava-Castro KE, Castro JI, Morales-Montor J. The role of cytokines in breast cancer development and progression. J Interferon Cytokine Res. 2015;35:1–16.
  5. Narita D, Seclaman E, Ursoniu S, Ilina R, Cireap N, Anghel A. Expression of CCL18 and interleukin-6 in the plasma of breast cancer patients as compared with benign tumor patients and healthy controls. Rom J Morphol Embryol. 2011;52:1261–1267.
  6. Alokail MS, Al-Daghri NM, Mohammed AK, Vanhoutte P, Alenad A. Increased TNF alpha, IL-6 and ErbB2 mRNA expression in peripheral blood leukocytes from breast cancer patients. Med Oncol. 2014;31:38.
  7. Todorovic-Rakovic N, Milovanovic J. Interleukin-8 in breast cancer progression. J Interferon Cytokine Res. 2013;33:563–570.
  8. Katanov C, Lerrer S, Liubomirski Y, et al. Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-alpha and the NF-kappaB pathway. Stem Cell Res Ther. 2015;6:87.
  9. Deshmukh SK, Srivastava SK, Bhardwaj A, et al. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation. Oncotarget. 2015;6:11231–11241.
  10. Yao C, Lin Y, Ye CS, Bi J, Zhu YF, Wang SM. Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer. Chin Med J (Engl). 2007;120:1766–1772.
  11. Sanguinetti A, Santini D, Bonafe M, Taffurelli M, Avenia N. Interleukin-6 and pro inflammatory status in the breast tumor microenvironment. World J Surg Oncol. 2015;13:129.
  12. Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE, Hall BM. Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J. 2007;21:3763–3770.
  13. Saglam O, Unal ZS, Subasi C, Ulukaya E, Karaoz E. IL-6 originated from breast cancer tissue-derived mesenchymal stromal cells may contribute to carcinogenesis. Tumour Biol. 2015;36:5667–5677.
  14. Di GH, Liu Y, Lu Y, Liu J, Wu C, Duan HF. IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells. PLoS One. 2014;9:e113572.
  15. Kozlowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz MZ. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz Akad Med Bialymst. 2003;48:82–84.
  16. Kornasiewicz O, Grat M, Dudek K, Lewandowski Z, Gorski Z, Zieniewicz K, Krawczyk M. Serum levels of HGF, IL-6, and TGF-alpha after benign liver tumor resection. Adv Med Sci. 2015;60:173–177.
  17. Zhou XL, Fan W, Yang G, Yu MX. The clinical significance of PR, ER, NF- kappa B, and TNF- alpha in breast cancer. Dis Markers. 2014;2014:494581.
  18. Schillace RV, Skinner AM, Pommier RF, et al. Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations. BMC Cancer. 2014;14:733.
  19. Markkula A, Simonsson M, Ingvar C, Rose C, Jernstrom H. IL6 genotype, tumour ER-status, and treatment predicted disease-free survival in a prospective breast cancer cohort. BMC Cancer. 2014;14:759.
  20. Di MG, Bellazzo A, Dal Ferro M, et al. Mutant p53 reprograms TNF signaling in cancer cells through interaction with the tumor suppressor DAB2IP. Mol Cell. 2014;56:617–629.
  21. Ma Y, Xiang D, Sun J, et al. Targeting of antigens to B lymphocytes via CD19 as a means for tumor vaccine development. J Immunol. 2013;190:5588–5899.
  22. Mohamed MM, El-Ghonaimy EA, Nouh MA, Schneider RJ, Sloane BF, El-Shinawi M. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties. Int J Biochem Cell Biol. 2014;46:138–147.
  23. Rathore AS, Kumar S, Konwar R, Makker A, Negi MP, Goel MM. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast. Indian J Med Res. 2014;140:361–369.
  24. Shiri S, Alizadeh AM, Baradaran B, et al. Dendrosomal curcumin suppresses metastatic breast cancer in mice by changing m1/m2 macrophage balance in the tumor microenvironment. Asian Pac J Cancer Prev. 2015;16:3917–3922.
  25. Zhou N, Zhang Y, Zhang X, et al. Exposure of tumor-associated macrophages to apoptotic mcf-7 cells promotes breast cancer growth and metastasis. Int J Mol Sci. 2015;16:11966–11982.
  26. Chavey C, Bibeau F, Gourgou-Bourgade S, et al. Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res. 2007;9:R15.
  27. Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications. Mol Biol Int. 2014;2014:852748.
  28. Murray RZ, Stow JL. Cytokine secretion in macrophages: SNAREs, rabs and membrane trafficking. Front Immunol. 2014;5:538.
  29. Rego SL, Helms RS, Dreau D. Tumor necrosis factor-alpha-converting enzyme activities and tumor-associated macrophages in breast cancer. Immunol Res. 2014;58:87-100.
  30. Jewett KA, Krueger JM. Humoral sleep regulation; interleukin-1 and tumor necrosis factor. Vitam Horm. 2012;89:241–257.