Expressions of IL-17 and TNF-α in patients with Hashimoto’s disease combined with thyroid cancer before and after surgery and their relationship with prognosis



This study aimed to investigate expressions and clinical significance of IL-17 and TNF-α after surgery in patients with Hashimoto’s disease (HD) combined with thyroid cancer (TC).

Patients and methods

From June 2010 to October 2012, 38 patients with HD combined with TC admitted to the oncology department of Tongji Hospital were selected as an experimental group, including three males and 35 females, aged 24–78 years. Forty adults undergoing physical examination during the same period were selected as a control group. All patients in the experimental group were given total endoscopic TC resection. Real-time fluorescence quantification (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of serum IL-17 and TNF-α before and 14 days after surgery. Patients with HD combined with TC were divided into high and low expression groups according to the median values of preoperative IL-17 mRNA and TNF-α mRNA. The relationship between IL-17, TNF-α, and prognosis of patients was analyzed through K-M survival curve.


The concentrations of IL-17 and TNF-α in serum were also higher than those in control group 14 days after surgery (p < 0.05). qRT-PCT showed that the relative expressions of IL-17 and TNF-α in serum 14 days after surgery were higher than those in control group (p < 0.05). According to the relative expression median of mRNA in IL-17 and TNF-α before surgery, they were divided into high and low expression groups. It was found that the survival rate of high expression groups of IL-17 and TNF-α was lower than that of low expression groups (IL-17, p = 0.028; TNF-α, p = 0.014).


The protein and mRNA of IL-17 and TNF-α in serum of HD patients with TC are higher than those of healthy control group. Expressions of IL-17 and TNF-α can be reduced by surgical resection of focal tissue. IL-17 and TNF-α may be used as potential prognostic indicators of HD patients with TC.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Torimoto K, Okada Y, Nakayamada S, Kubo S, Tanaka Y. Anti-PD-1 antibody therapy induces Hashimoto’s disease with an increase in peripheral blood follicular helper T cells. Thyroid. 2017;27:1335–6.

    CAS  Article  Google Scholar 

  2. 2.

    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  Google Scholar 

  3. 3.

    Strickland KC, Howitt BE, Marqusee E, Alexander EK, Cibas ES, Krane JF, Barletta JA. The impact of noninvasive follicular variant of papillary thyroid carcinoma on rates of malignancy for fine-needle aspiration diagnostic categories. Thyroid. 2015;25:987–92.

    Article  Google Scholar 

  4. 4.

    Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.

    CAS  Article  Google Scholar 

  5. 5.

    Mestman JH. Fetal hyperthyroidism resulted from TSI in a mother with Hashimoto’s hypothyroidism. Clin Thyroidol. 2017;29:32–4.

    Article  Google Scholar 

  6. 6.

    La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F, Negri E. Thyroid cancer mortality and incidence: a global overview. Int J Cancer. 2015;136:2187–95.

    Article  Google Scholar 

  7. 7.

    Boi F, Pani F, Calo PG, Lai ML, Mariotti S. High prevalence of papillary thyroid carcinoma in nodular Hashimoto’s thyroiditis at the first diagnosis and during the follow-up. J Endocrinol Investig. 2018;41:395–402.

    CAS  Article  Google Scholar 

  8. 8.

    Gaffen S. IL-17 receptor composition. Nat Rev Immunol. 2015;16:4.

    Article  Google Scholar 

  9. 9.

    Akitsu A, Ishigame H, Kakuta S, Chung SH, Ikeda S, Shimizu K, Kubo S, Liu Y, Umemura M, Matsuzaki G, Yoshikai Y, Saijo S, Iwakura Y. IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+ Vγ6+ γδ T cells. Nat Commun. 2015;6:7464.

    CAS  Article  Google Scholar 

  10. 10.

    De Simone V, Franze E, Ronchetti G, Colantoni A, Fantini MC, Di Fusco D, Sica GS, Sileri P, MacDonald TT, Pallone F, Monteleone G, Stolfi C. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene. 2015;34:3493–503.

    Article  Google Scholar 

  11. 11.

    Wu P, Baker JR. Apoptosis in autoimmune thyroid disease. In: Rapoport B, McLachlan SM, editors. Graves’ disease. MA: Springer; 2000. pp. 107–126.

  12. 12.

    Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.

    Article  Google Scholar 

  13. 13.

    Cancer Genome Atlas Program Office. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159:676–90.

    Article  Google Scholar 

  14. 14.

    Kim J, Bang Y, Lee WJ. Living near nuclear power plants and thyroid cancer risk: a systematic review and meta-analysis. Environ Int. 2016;87:42–8.

    Article  Google Scholar 

  15. 15.

    Zayed AA, Ali MK, Jaber OI, Suleiman MJ, Ashhab AA, Al Shweiat WM, Momani MS, Shomaf M, AbuRuz SM. Is Hashimoto’s thyroiditis a risk factor for medullary thyroid carcinoma? Our experience and a literature review. Endocrine. 2015;48:629–36.

    CAS  Article  Google Scholar 

  16. 16.

    Huang TC, Cheng YK, Chen TW, Hsu YC, Liu EW, Chen HH. A ‘silent’skull metastatic follicular thyroid carcinoma mimicking as a benign scalp tumor in a pregnant woman. Endocrinol Diabetes Metab Case Rep. 2017;2017:16.

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol. 2014;170:R241–R252252.

    CAS  Article  Google Scholar 

  18. 18.

    Girardi FM, Barra MB, Zettler CG. Papillary thyroid carcinoma: does the association with Hashimoto’s thyroiditis affect the clinicopathological characteristics of the disease? Braz J Otorhinolaryngol. 2015;81:283–7.

    Article  Google Scholar 

  19. 19.

    Chang SH, Mirabolfathinejad SG, Katta H, Cumpian AM, Gong L, Caetano MS, Moghaddam SJ, Dong C. T helper 17 cells play a critical pathogenic role in lung cancer. Proc Natl Acad Sci USA. 2014;111:5664–9.

    CAS  Article  Google Scholar 

  20. 20.

    Seguin L, Desgrosellier JS, Weis SM, Cheresh DA. Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance. Trends Cell Biol. 2015;25:234–40.

    CAS  Article  Google Scholar 

  21. 21.

    Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJM, Ciampricotti M, Hawinkels LJAC, Jonkers J, de Visser KE. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015;522:345–8.

    CAS  Article  Google Scholar 

  22. 22.

    Bär E, Whitney PG, Moor K, Reis e Sousa C, LeibundGut-Landmann S. IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells. Immunity. 2014;40:117–27.

    Article  Google Scholar 

  23. 23.

    Li D, Cai W, Gu R, Zhang Y, Zhang H, Tang K, Xu P, Katirai F, Shi W, Wang L, Huang T, Huang B. Th17 cell plays a role in the pathogenesis of Hashimoto’s thyroiditis in patients. Clin Immunol. 2013;149:411–20.

    CAS  Article  Google Scholar 

  24. 24.

    Jiang XL, Zhang H, Chen YL, Peng L. Expression of microRNA-221 and IL-17 in papillary thyroid carcinoma and correlation with clinicopathologic features. Zhonghua Bing Li Xue Za Zhi=Chin J Pathol. 2017;46:160–5.

    CAS  Google Scholar 

  25. 25.

    Kobawala TP, Trivedi TI, Gajjar KK, Patel DH, Patel GH, Ghosh NR. Significance of TNF-α and the adhesion molecules: l-selectin and VCAM-1 in papillary thyroid carcinoma. J Thyroid Res. 2016;2016:8143695.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Díez JJ, Hernanz A, Medina S, Bayón C, Iglesias P. Serum concentrations of tumour necrosis factor-alpha (TNF-α) and soluble TNF-α receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function. Clin Endocrinol. 2002;57:515–21.

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to L. Xu.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

The study was approved by Ethical Committee of Tongji Hospital and conducted in accordance with the ethical standards.

Informed consent

All participants provided informed consent prior to their participation.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, N., Wang, Q., Tian, Y. et al. Expressions of IL-17 and TNF-α in patients with Hashimoto’s disease combined with thyroid cancer before and after surgery and their relationship with prognosis. Clin Transl Oncol 22, 1280–1287 (2020).

Download citation


  • IL-17
  • TNF-α
  • Hashimoto’s disease
  • Thyroid cancer
  • Prognosis