open access

Vol 73, No 2 (2023)
Research paper (original)
Published online: 2023-04-27
Get Citation

Histophysiology study of interleukin-4 in thyroid cancer patients

Ali Reda Hussein1, Dhamia Kasim Suker2, Sanaa Jameel Thamer2, Majid Hameed Alabbood3
·
Nowotwory. Journal of Oncology 2023;73(2):73-80.
Affiliations
  1. Ph.D. student, Physiology, Biology Department, College of Sciences, Basrah University, Basrah, Iraq
  2. Biology Department, College of Sciences, Basrah University, Basrah, Iraq
  3. Alzahraa College of Medicine, Basrah University, Basrah, Iraq

open access

Vol 73, No 2 (2023)
Original article
Published online: 2023-04-27

Abstract

Introduction.Interleukins have promising prospects in the clinical treatment of cancer. Interleukin-4 (IL-4) is an an­ti-inflammatory cytokine with an immunosuppressive effect on antitumor activity by immune cells, but the mechanical action of IL-4 in thyroid cancer is unknown. Aim: to investigate the effect of IL-4 expression in thyroid cancer patients. Furthermore, to clarify the association between obesity and thyroid cancer.

Material and methods.The present study was conducted on 115 subjects with thyroid nodules (36 with thyroid cancer and 79 with benign lesions) in Basrah, Iraq, from November 2019 to April 2022. To conduct a histophysiology study of IL-4.

Results.There was a significant difference in serum IL-4 between the thyroid cancer and control subjects. A higher level of serum IL-4 was observed in the Hashimoto thyroiditis group. There was no significant difference in body mass index (BMI) between thyroid cancer and control subjects. The expression of tissue IL-4 in thyroid cancer patients was strong in 8 (22.22%) slides, moderate in 7 slides (19.44%), weak in 8 slides (22.22%), and negative in 13 slides (36.11%), while in the control group, it was strong in 7 (30.44%) slides, moderate in 8 slides (34.79%), weak in 5 slides (21.74%) and neg­ative in 3 slides (13.03%).

Conclusions.These findings indicate that serum levels of IL-4 may help diagnose thyroid cancer and identify patients with active disease who deserve closer medical attention. Furthermore, the secretion of IL-4 was systematic and not localized in thyroid cancer tissues. Obesity was not associated with a prevalence of thyroid cancer.

Abstract

Introduction.Interleukins have promising prospects in the clinical treatment of cancer. Interleukin-4 (IL-4) is an an­ti-inflammatory cytokine with an immunosuppressive effect on antitumor activity by immune cells, but the mechanical action of IL-4 in thyroid cancer is unknown. Aim: to investigate the effect of IL-4 expression in thyroid cancer patients. Furthermore, to clarify the association between obesity and thyroid cancer.

Material and methods.The present study was conducted on 115 subjects with thyroid nodules (36 with thyroid cancer and 79 with benign lesions) in Basrah, Iraq, from November 2019 to April 2022. To conduct a histophysiology study of IL-4.

Results.There was a significant difference in serum IL-4 between the thyroid cancer and control subjects. A higher level of serum IL-4 was observed in the Hashimoto thyroiditis group. There was no significant difference in body mass index (BMI) between thyroid cancer and control subjects. The expression of tissue IL-4 in thyroid cancer patients was strong in 8 (22.22%) slides, moderate in 7 slides (19.44%), weak in 8 slides (22.22%), and negative in 13 slides (36.11%), while in the control group, it was strong in 7 (30.44%) slides, moderate in 8 slides (34.79%), weak in 5 slides (21.74%) and neg­ative in 3 slides (13.03%).

Conclusions.These findings indicate that serum levels of IL-4 may help diagnose thyroid cancer and identify patients with active disease who deserve closer medical attention. Furthermore, the secretion of IL-4 was systematic and not localized in thyroid cancer tissues. Obesity was not associated with a prevalence of thyroid cancer.

Get Citation

Keywords

thyroid cancer; IL-4; obesity; thyroid gland; histophysiology

About this article
Title

Histophysiology study of interleukin-4 in thyroid cancer patients

Journal

Nowotwory. Journal of Oncology

Issue

Vol 73, No 2 (2023)

Article type

Research paper (original)

Pages

73-80

Published online

2023-04-27

Page views

1829

Article views/downloads

180

DOI

10.5603/NJO.2023.0017

Bibliographic record

Nowotwory. Journal of Oncology 2023;73(2):73-80.

Keywords

thyroid cancer
IL-4
obesity
thyroid gland
histophysiology

Authors

Ali Reda Hussein
Dhamia Kasim Suker
Sanaa Jameel Thamer
Majid Hameed Alabbood

References (55)
  1. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2007. CA Cancer J Clin. 2007; 57(1): 43–66.
  2. Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog. 2013; 18(1-2): 43–73.
  3. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002; 2(8): 563–572.
  4. American Cancer Society. Cancer Facts & Figures 2021. Atlanta: 2021. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2021.html.
  5. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26(1): 1–133.
  6. Fallahi P, Mazzi V, Vita R, et al. New therapies for dedifferentiated papillary thyroid cancer. Int J Mol Sci. 2015; 16(3): 6153–6182.
  7. Mironska A, Łukaszewicz-Zajac M, Mroczko B. Clinical Significance of Selected Chemokines in Thyroid Cancer. Anticancer Res. 2019; 39(6): 2715–2720.
  8. Zhang GQ, Shen CT, Song HJ, et al. High Expression of Interleukin-12A and Its Association with the Clinicopathology and Prognosis of Differentiated Thyroid Cancer. Eur Thyroid J. 2020; 9(3): 139–147.
  9. Karagiannis AK, Philippou A, Tseleni-Balafouta S, et al. IGF-IEc Expression Is Associated With Advanced Differentiated Thyroid Cancer. Anticancer Res. 2019; 39(6): 2811–2819.
  10. Guth S, Theune U, Aberle J, et al. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest. 2009; 39(8): 699–706.
  11. Bernet VJ, Chindris AM. Update on the Evaluation of Thyroid Nodules. J Nucl Med. 2021; 62(Suppl 2): 13S–19S.
  12. Al-Subaiee I, Al-Rikaby H. Prevalence of thyroid incidentaloma detected by high-resolution ultrasound and their potential risk of malignancy in healthy individuals in Basrah Province. Medical Journal of Babylon. 2019; 16(3): 252.
  13. Mansour A, Alhamza AA, Almomin AA, et al. SUN-418 Patterns of Thyroid Disease in Basrah, Iraq. Retrospective Study. Journal of the Endocrine Society. 2020; 4(Supplement_1).
  14. Liu H, Lin F. Application of immunohistochemistry in thyroid pathology. Arch Pathol Lab Med. 2015; 139(1): 67–82.
  15. Martins MB, Marcello MA, Batista Fd, et al. Serum interleukin measurement may help identify thyroid cancer patients with active disease. Clin Biochem. 2018; 52: 1–7.
  16. Holder PG, Lim SA, Huang CS, et al. Engineering interferons and interleukins for cancer immunotherapy. Adv Drug Deliv Rev. 2022; 182: 114112.
  17. Hoon DS, Banez M, Okun E, et al. Modulation of human melanoma cells by interleukin-4 and in combination with gamma-interferon or alpha-tumor necrosis factor. Cancer Res. 1991; 51(8): 2002–2008.
  18. Cunha LL, Morari EC, Nonogaki S, et al. Interleukin 10 expression is related to aggressiveness and poor prognosis of patients with thyroid cancer. Cancer Immunol Immunother. 2017; 66(2): 141–148.
  19. Xi C, Zhang GQ, Sun ZK, et al. Interleukins in Thyroid Cancer: From Basic Researches to Applications in Clinical Practice. Front Immunol. 2020; 11: 1124.
  20. Vella V, Mineo R, Frasca F, et al. Interleukin-4 stimulates papillary thyroid cancer cell survival: implications in patients with thyroid cancer and concomitant Graves' disease. J Clin Endocrinol Metab. 2004; 89(6): 2880–2889.
  21. NIH. National Heart, Lung and Blood Institute. Calculate the Body Mass Index. 2022. https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm.
  22. Immunohistochemistry and Immunocytochemistry: Essential Methods. 2017.
  23. Choudhury KR, Yagle KJ, Swanson PE, et al. A robust automated measure of average antibody staining in immunohistochemistry images. J Histochem Cytochem. 2010; 58(2): 95–107.
  24. Rao J, Kish L. Survey Sampling. Biometrics. 1969; 25(3): 603.
  25. IBM. IBM SPSS Advanced Statistics 24. 2019.
  26. Suzuki A, Leland P, Joshi BH, et al. Targeting of IL-4 and IL-13 receptors for cancer therapy. Cytokine. 2015; 75(1): 79–88.
  27. Zivancevic-Simonovic S, Mihaljevic O, Majstorovic I, et al. Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis. Cancer Immunol Immunother. 2015; 64(8): 1011–1019.
  28. Safi S, Yamauchi Y, Hoffmann H, et al. Circulating Interleukin-4 Is Associated with a Systemic T Cell Response against Tumor-Associated Antigens in Treatment-Naïve Patients with Resectable Non-Small-Cell Lung Cancer. Cancers (Basel). 2020; 12(12).
  29. Todaro M, Zerilli M, Ricci-Vitiani L, et al. Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth of thyroid cancer cells. Cancer Res. 2006; 66(3): 1491–1499.
  30. Li Z, Jiang J, Wang Z, et al. Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis. Cancer Res. 2008; 68(21): 8687–8694.
  31. Martins MB, de Assis Batista F, Bufalo NE, et al. Polymorphisms of IL-4 and IL-4R are associated to some demographic characteristics of differentiated thyroid cancer patients but are not determinants of risk in the Brazilian population. Endocrine. 2021; 72(2): 470–478.
  32. Giermasz AS, Urban JA, Nakamura Y, et al. Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines. Cancer Immunol Immunother. 2009; 58(8): 1329–1336.
  33. Eguchi J, Kuwashima N, Hatano M, et al. IL-4-transfected tumor cell vaccines activate tumor-infiltrating dendritic cells and promote type-1 immunity. J Immunol. 2005; 174(11): 7194–7201.
  34. Noffz G, Qin Z, Kopf M, et al. Neutrophils but Not Eosinophils Are Involved in Growth Suppression of IL-4-Secreting Tumors. J Immunol. 1998; 160(1): 345–350.
  35. Street NE, Mosmann TR. IL4 and IL5: the role of two multifunctional cytokines and their place in the network of cytokine interactions. Biotherapy. 1990; 2(4): 347–362.
  36. Colledge NR, Walker BR, Ralston SH. Davidson ’ s Principles and Practice of Medicine, 21st ed. Edinburgh Churchill Livingstone/Elsevier, London 2010.
  37. Thomson AW, Lotze MT. The Cytokine Handbook, 4 ed., vol. I. Elsevier 2003.
  38. Schuetz M, Duan H, Wahl K, et al. T lymphocyte cytokine production patterns in Hashimoto patients with elevated calcitonin levels and their relationship to tumor initiation. Anticancer Res. 2006; 26(6B): 4591–4596.
  39. Mustafa MA, Malenie R, Mir F, et al. Malignant effusions secondary to metastatic thyroid carcinomas: A review of 15 cases. Cancer Cytopathol. 2023; 131(2): 136–143.
  40. Al-Atrooshi SAM, Ibraheem NH, Yahya TT. The Prevalence of Papillary Thyroid Microcarcinoma in 489 Cases of Thyroidectomy in Iraqi Patients. Iraqi Postgraduate Medical Journal. 2017; 16(2): 151–158.
  41. Kadhim A, Kadhim MA, Ahmed BS, et al. The frequency of thyroid carcinoma in patients with solitary and multiple nodules utilizing ultrasound guided fine needle aspiration cytology (FNAC): A prospective study (Thyroid carcinoma and U / S guided FNA). J Fac Med Baghdad. 2010; 52(2): 134–138.
  42. NHLBI. Managing Overweight and Obesity in Adults: Systematic Evidence Review from the Obesity Expert Panel. 2021: 501. https://www.nhlbi.nih.gov/sites/default/files/media/docs/obesity-evidence-review.pdf.
  43. Han JiM, Kim TY, Jeon MJi, et al. Obesity is a risk factor for thyroid cancer in a large, ultrasonographically screened population. Eur J Endocrinol. 2013; 168(6): 879–886.
  44. Masone S, Velotti N, Savastano S, et al. Morbid Obesity and Thyroid Cancer Rate. A Review of Literature. J Clin Med. 2021; 10(9): 1894.
  45. He Q, Sun H, Li F, et al. Obesity and risk of differentiated thyroid cancer: A large-scale case-control study. Clin Endocrinol (Oxf). 2019; 91(6): 869–878.
  46. Rotondi M, Castagna MG, Cappelli C, et al. Obesity Does Not Modify the Risk of Differentiated Thyroid Cancer in a Cytological Series of Thyroid Nodules. Eur Thyroid J. 2016; 5(2): 125–131.
  47. Ramdass V, Caskey E, Sklarz T, et al. Association Between Obesity and Cancer Mortality: An Internal Medicine Outpatient Clinic Perspective. J Clin Med Res. 2021; 13(7): 377–386.
  48. Gąsior-Perczak D, Pałyga I, Szymonek M, et al. The impact of BMI on clinical progress, response to treatment, and disease course in patients with differentiated thyroid cancer. PLoS One. 2018; 13(10): e0204668.
  49. Chung YC, Chaen YL, Hsu CP. Clinical significance of tissue expression of interleukin-6 in colorectal carcinoma. Anticancer Res. 2006; 26(5B): 3905–3911.
  50. de Oliveira MV, Fraga CA, Gomez RS, et al. Immunohistochemical expression of interleukin-4, -6, -8, and -12 in inflammatory cells in surrounding invasive front of oral squamous cell carcinoma. Head Neck. 2009; 31(11): 1439–1446.
  51. Wang TY, Chen KY, Jhan KY, et al. Temporal-spatial expressions of interleukin-4, interleukin-10, and interleukin-13 in the brains of C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis: An immunohistochemical study. J Microbiol Immunol Infect. 2020; 53(4): 592–603.
  52. Salmon-Ehr V, Ramont L, Godeau G, et al. Implication of interleukin-4 in wound healing. Lab Invest. 2000; 80(8): 1337–1343.
  53. Abbas EK. Molecular and gene expression study of interleukin-6 (IL-6)in patients with cancer cachexia syndrome. Basrah. 2017.
  54. Suker DK, Badran AI, Abbas EK, et al. Immunohistochemistry Analysis for Interleukin-6 Expression from the Tumor Tissue. International Journal of Sciences. 2017; 3(03): 14–24.
  55. Obiri NI, Siegel JP, Varricchio F, et al. Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells. Clin Exp Immunol. 1994; 95(1): 148–155.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl