The association between mRNA expression of resistin, TNF- α, IL-6, IL-8, and ER-α in peripheral blood mononuclear cells and breast cancer

The association between mRNA expression of resistin, TNF- α, IL-6, IL-8, and ER-α in peripheral blood mononuclear cells and breast cancer

Background/aim: Adipocytokines, adipose tissue-derived proteins, were demonstrated to be involved in the pathogenesis of breast cancer. We assessed the mRNA expression of resistin, tumor necrosis factor-alpha (TNF-α), interleukins 6 and 8 (IL-6, and IL-8), and estrogen receptor alpha (ER-α) in peripheral blood mononuclear cells (PBMCs) of women with and without breast cancer. Materials and methods: The PBMCs were isolated from the whole blood of 32 women with breast cancer and 18 women without breast cancer using density gradient centrifugation. The mRNA expression of the target genes was measured by reverse-transcription polymerase chain reaction (RT-PCR). Body mass index was calculated, additionally, clinicopathological characteristics of the breast cancer patients were determined by histopathological examination. Results: The mRNA expression of resistin (3.5-fold) and IL-6 (15-fold) in PBMCs of breast cancer patients significantly increased in comparison to healthy controls. Resistin expression was significantly associated with inflammatory markers including TNF-α, IL-6, IL-8, but not with anthropometric indices. Logistic regression analysis revealed the studied adipokines were not associated with breast cancer. Based on the ROC curve analysis the diagnostic performance of IL-6 was significant (0.825, 95% CI: 0.549-0.94, p = 0.030), thus, it might be considered as a breast cancer biomarker that reflecting an early and inflammatory stage of the disease. Conclusion: Breast cancer is not associated with increased expression of inflammatory cytokines in PBMCs. Our results suggested that a PBMC-based gene expression test may be developed to detect breast cancer early.Key words: Breast cancer, resistin, tumor necrosis factor-alpha, interleukin-6, interleukin-8, estrogen receptor alpha

___

  • 1. Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global cancer in women: burden and trends. Cancer Epidemiology, Biomarkers & Prevention 2017; 26 (4): 444-457. doi: 10.1158/1055-9965.EPI-16-0858
  • 2. Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obesity Reviews 2004; 5 (3):153-65. doi:10.1111/j.1467-789X.2004. 00142.x
  • 3. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR et al. The hormone resistin links obesity to diabetes. Nature 2001;409(6818):307–312. doi: 10.1038/35053000
  • 4. Salageanu A, Tucureanu C, Lerescu L, Caras I, Pitica R et al. Serum levels of adipokines resistin and leptin in patients with colon cancer. Journal of Medicine and life 2010;3(4):416–420.
  • 5. Housa D, Vernerova Z, Heracek J, Cechak P, Rosova B et al. Serum resistin levels in benign prostate hyperplasia and nonmetastatic prostate cancer: possible role in cancer progression. Neoplasma 2008;55(5):442–446.
  • 6. Hlavna M, Kohut L, Lipkova J, Bienertova-Vasku J, Dostalova Z et al. Relationship of resistin levels with endometrial cancer risk. Neoplasma 2011;58(2):124–128. doi: 10.4149/ neo_2011_02_124
  • 7. Assiri Adel-MA, Kamel Hala-FM, Hassanien MohamedFR. Resistin, Visfatin, Adiponectin, and Leptin: Risk of Breast Cancer in Pre- and Postmenopausal Saudi Females and Their Possible Diagnostic and Predictive Implications as Novel Biomarkers. Disease Markers 2015; 2015:253519. doi: 10.1155/2015/253519
  • 8. Himmerich H, Fulda S, Linseisen J, Seiler H, Wolfram G et al. TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general population. European Cytokine Network 2006; 17 (3):196–201.
  • 9. De Mello VD, Kolehmainen M, Schwab U, Mager U, Laaksonen DE et al. Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. Metabolism 2008; 57:192–199. doi: 10.1016/j.metabol.2007.08.024
  • 10. Kishimoto T. Interleukin-6: from basic science to medicine – 40 years in immunology. Annual Review of Immunology 2005; 23:1–21. doi: 10.1146/annurev.immunol.23.021704.115806
  • 11. Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine and Growth Factor Reviews 2002; 13(4–5):357–368. doi: 10.1016/s1359- 6101(02)00027-8
  • 12. Esquivel-Velázquez M, Ostoa-Saloma P, Palacios-Arreola MI, Nava-Castro KE, Ivonne Castro J, Morales-Montor J. The Role of Cytokines in Breast Cancer Development and Progression. Journal of Interferon and Cytokine Research 2015; 35(1): 1–16. doi: 10.1089/jir.2014.0026
  • 13. Salgado R, Junius S, Benoy I, Van Dam P, Vermeulen P et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. International Journal of Cancer 2003; 103:642-646. doi:10.1002/ijc.10833
  • 14. Knüpfer H, Preiss R. Significance of interleukin-6 (IL-6) in breast cancer (review). Breast Cancer Research and Treatment 2007; 102(2):129–135. doi: 10.1007/s10549-006-9328-3
  • 15. Todorovic-Rakovic N, Milovanovic J. Interleukin-8 in breast cancer progression. Journal of Interferon and Cytokine Research 2013; 33(10):563–570. doi: 10.1089/jir.2013.0023
  • 16. Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 2004; 6(5):447–458. doi: 10.1016/j.ccr.2004.09.028
  • 17. Andres PJ, Illera JC, Caceres S, Diez L, Perez-Alenza MD et al. Increased levels of interleukins 8 and10 as findings of canineinflammatory mammary cancer. Veterinary Immunology and Immunopathology 2013;152(3-4):245–51. doi: 10.1016/j.vetimm.2012.12.010
  • 18. Lin Y, Huang R, Chen L, Li S, Shi Q et al. Identification of interleukin-8 as estrogen receptor-regulated factor involved in breast cancer invasion and angiogenesis by protein arrays. International Journal of Cancer 2004;109(4):507–515. doi: 10.1002/ijc.11724
  • 19. Kanda N, Tamaki K. Estrogen enhances immunoglobulin production by human PBMCs. Journal of Allergy and Clinical Immunology 1999; 103 (2 Pt 1):282–288. doi: 10.1016/s0091- 6749(99)70503-8
  • 20. McMurray RW, Ndebele K, Hardy KJ, Jenkins JK. 17-betaestradiol suppresses IL-2 and IL-2 receptor. Cytokine 2001; 14 (6):324–333. doi: 10.1006/cyto.2001.0900
  • 21. Lee YC, Chen YJ, Wu CC, Lo S, Hou MF et al. Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification. Gynecologic Oncology 2012; 125 (3) :742-750. doi: 10.1016/j.ygyno.2012.02.032
  • 22. Sharma P, Sahni NS, Tibshirani R, Skaane P, Urdal P et al. Early detection of breast cancer based on gene-expression patterns in peripheral blood cells. Breast Cancer Research 2005;7(5): R634-44. doi: 10.1186/bcr1203
  • 23. Chen S, Liu M, Liang B, Ge S, Peng J et al. Identification of human peripheral blood monocyte gene markers for early screening of solid tumors. PLoS One 2020; 30;15(3): e0230905. doi: 10.1371/journal.pone.0230905
  • 24. Dalamaga M, Sotiropoulos G, Karmaniolas K, Pelekanos N, Papadavid E et al. Serum resistin: a biomarker of breast cancer in postmenopausal women? Association with clinicopathological characteristics, tumor markers, inflammatory and metabolic parameters. Clinical Biochemistry 2013; 46 (7-8) :584-590. doi: 10.1016/j.clinbiochem.2013.01.001
  • 25. Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology (Williston Park) 2002; 16 (2): 217-226.
  • 26. O’Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy. British Journal of Cancer 2001; 85 (4): 473-483. doi: 10.1054/bjoc.2001.1943
  • 27. Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE et al. Interleukin-6 is a potent growth factor for ER-a-positive human breast cancer. The FASEB Journal 2007; 21(13):3763– 3770. doi: 10.1096/fj.07-8832com
  • 28. Hiba Q. Ali, Nadham K. Mahdi, Mohammad H. Al-Jowher. Serum Ig and Cytokine Levels in Women with Breast Cancer Before and After Mastectomy. Medical Journal of Islamic World Academy of Sciences 2012; 20(4): 121-129.
  • 29. Chala E, Manes C, Iliades H, Skaragkas G, Mouratidou D et al. Insulin resistance, growth factors and cytokine levels in overweight women with breast cancer before and after chemotherapy. Hormones (Athens) 2006; 5 (2):137-146. doi: 10.14310/horm.2002.11177
  • 30. Yokoe T, Iino Y, Morishita Y. Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report. Breast Cancer 2000; 7 (3):187-190. doi: 10.1007/BF02967458
  • 31. Conze D, Weiss L, Regen P S, Bhushan A, Weaver D et al. Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells. Cancer Research 2001; 61(24):8851-8858.
  • 32. Shi Z, Yang WM, Chen LP, Yang DH, Zhou Q et al. Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production. Breast Cancer Research and Treatment 2012;135(3):737-747. doi: 10.1007/s10549-012-2196-0
  • 33. Abłonska E, Kiluk M, Markiewicz W, Piotrowski L, Grabowska Z et al. TNF-a, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients. Archivum immunologiae et therapiae experimentalis (Warsz) 2001; 49 (1):63-69.
  • 34. Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC. Dual role of tumor necrosis factor-alpha in angiogenesis. The American Journal of Pathology 1992;140 (3): 539-544.
  • 35. Rivas MA, Carnevale RP, Proietti CJ, Rosemblit C, Beguelin W et al. TNF alpha acting on TNFR1 promotes breast cancer growth via P42/P44 MAPK, JNK, Akt and NF-Kappa B-dependent pathways. Experimental Cell Research 2008; 314 (3):509-529. doi: 10.1016/j.yexcr.2007.10.005
  • 36. Chen X, ShuY, LiW, et al. TNF-alpha-induced metastasis gene changes in MCF-7 cells. Journal of Nanjing Medical University 2008; 22 (6):366-371. doi: 10.1016/S1007-4376(09)60008-3
  • 37. Zuccari DA, Leonel C, Castro R, Gelaleti GB, Jardim BV et al. An immunohistochemical study of interleukin-8 (IL-8) in breast cancer. Acta Histochemica 2012;114(6):571–5766. doi: 10.1016/j.acthis.2011.10.007
  • 38. Lyon DE, McCain NL, Walter J, Schubert C. Cytokine comparisons between women with breast cancer and women with a negative breast biopsy. Nursing Research 2008;57(1):51– 518. doi: 10.1097/01.NNR.0000280655.58266.6c
  • 39. Lee SH, Chung MA, Quddus MR, Steinhoff MM, Cady B. The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer. The American Journal of Surgery 2003; 186 (4): 348-350. doi: 10.1016/s0002-9610(03)00271-x
  • 40. Harvey JM, Clark GM, Osborne CK and Allred DC: Estrogen receptor status by immunohistochemistry is superior to the ligand binding assay for predicting response to adjuvant endocrine therapy in breast cancer. Journal of Clinical Oncology 1999; 17 (5): 1474-1481. doi: 10.1200/JCO.1999.17.5.1474
  • 41. Taucher S, Rudas M, Gnant M, Thomanek K, Dubsky P et al. Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy. Endocrine-related Cancer 2003; 10 (1): 91-98. doi: 10.1677/erc.0.0100091
  • 42. Bottini A, Berruti A, Bersiga A, Brunelli A, Brizzi MP et al. Effect of neoadjuvant chemotherapy on Ki-67 labelling index, c-erbB-2 expression and steroid hormone receptor status in human breast tumors. Anticancer Research 1996; 16 (5B):3105- 3110
  • 43. Hawkins RA, Tesdale AL, Anderson ED, Levack PA, Chetty U et al. Does the estrogen receptor concentration of a breast cancer change during systemic therapy? British Journal of Cancer 1990; 61 (6): 877-880. doi: 10.1038/bjc.1990.196
  • 44. Schneider J, Lucas R, Sanchez J, Ruibal A, Tejerina A et al. Modulation of molecular marker expression by induction chemotherapy in locally advanced breast cancer: correlation with the response to therapy and the expression of MDR1 and LRP. Anticancer Research 2000; 20 (6B): 4373-4377.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Impact of hospital-acquired acute kidney injury on Covid-19 outcomes in patients with and without chronic kidney disease: a multicenter retrospective cohort study

Mustafa ARICI, Nurhan SEYAHİ, Erkan ŞENGÜL, Kenan TURGUTALP, Mürşide Esra DÖLARSLAN, Savaş ÖZTÜRK, Feyza BORA, Tuba Elif ÖZLER, Yavuz AYAR, Ali Rıza ODABAŞ, Kenan ATEŞ, Ekrem KARA, Mehmet Rıza ALTIPARMAK, Savaş SİPAHİ, Serkan BAKIRDÖĞEN, Özkan GÜNGÖR, Hakkı ÇETİNKAYA, Zeki AYDIN, Zeki SOYPAÇACI, İdr

Popliteal artery aneurysms treatments: early midterm results of the use of endovascular stent grafts

Kaptanıderya TAYFUR, Mehmet Şenel BADEMCİ

Sequential analysis of single-center experience of living donor kidney transplants with several vascular anastomosis techniques

Mehmet VELİDEDEOĞLU, Kaya SARIBEYOĞLU, Salih PEKMEZCİ, Mehmet ELİÇEVİK, Metin KAPAN, Berrin Papila KUNDAKTEPE, Ali Vedat DURGUN, Ertuğrul GÖKSOY

Evaluation of schwannoma using the 3D-SPACE sequence: comparison with the 3D-CISS sequence in 3T-MRI

Murat UÇAR, İsmail AKDULUM, Enes GÜRÜN, Pınar KILIÇ, Nil TOKGÖZ

Point-of-care ultrasound assessment of the inferior vena cava distensibility index in mechanically ventilated children in the operating room

Faruk EKİNCİ, Ahmet YÖNTEM, Nagehan ASLAN, Dinçer YILDIZDAŞ, Özden ÖZGÜR HOROZ, Murat Türkeün ILGINEL, Demet LAFLI TUNAY

What is the consistency between the results of needle biopsy and prostatectomy specimen pathology results? A pilot study

Ömer Ozan YILDIZLI, İbrahim ÜNTAN, Deniz DEMİRCİ

The study of sirtuins in breast cancer patients before and after radiotherapy

Eser KILIÇ, Oğuz Galip YILDIZ, Hatice SARAÇOĞLU, Nazlı HELVACI

How safe are children with COVID-19 from cardiac risks? Pediatric risk assesment; insights from echocardiography and electrocardiography

Berna Şaylan ÇEVİK, Eda KEPENEKLİ, Şule ARICI, Nurhayat YAKUT, Zeynep ERGENÇ, Özge GÜNAL

Prognostic value of the C-reactive protein to albumin ratio in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction

Mehmet Mustafa CAN, Özgür SÖĞÜT, Tarık AKDEMİR

Points to consider when evaluating three-dimensional digital subtraction angiography of intracranial aneurysms and their effects on treatment

Yılmaz ÖNAL, Murat VELİOĞLU, Hakkı Muammer KARAKAŞ, İsmail YARDIMCIOĞLU