Korelasi antara Kadar Kalsidiol (25-Oh) dan Rasio Netrofil-Limfosit dengan Keganasan Nodul Tiroid

Authors

  • Bryan D. Bogar Universitas Sam Ratulangi
  • Nico Lumintang Universitas Sam Ratulangi
  • Sherly Tandililing Universitas Sam Ratulangi
  • Windy M. Wariki Universitas Sam Ratulangi

DOI:

https://doi.org/10.35790/ecl.v12i2.48492

Abstract

Abstract: Thyroid malignancy has shown the highest annual incidence rate. Vitamin D deficiency (serum 25-hydroxyvitamin D levels) is one of the risk factors for thyroid malignancy. The neutrophil-lymphocyte ratio (NLR) reflects the balance between pro-tumor inflammatory response and anti-tumor immune response. This study aimed to investigate the relationship between serum 25-hydroxyvitamin D levels, NLR, and thyroid nodule malignancy. This was an observational and analytical study with cross-sectional design. Samples were patients with thyroid nodules admitted to Prof. Dr. R. D. Kandou Hospital, Manado, form August 2022 to March 2023. The results obtained a total of 46 patients with thyroid malignancy that  met the inclusion criteria. The patient characteristics were predominantly female (82.6%), with a mean age of 50.2 ± 14.74 years, normal thyroid hormone status (82.6%), mean serum 25-hydroxyvitamin D levels of 32.25 ng/mL, mean NLR of 5, and papillary carcinoma as the most common malignancy (43.48%). Spearman's correlation analysis revealed a significant association between thyroid malignancy and serum 25-hydroxyvitamin D levels (r =-0.501, p=0) as well as NLR (r 0.376, p=0.01). In conclusion, serum 25-hydroxyvitamin D levels and NLR can be used as indicators for predicting thyroid nodule malignancy.

Keywords: thyroid malignancy; 25-hydroxyvitamin D; neutrophil-lymphocyte ratio

 

Abstrak: Keganasan tiroid mengalami peningkatan angka kejadian tertinggi pertahun. Kekurangan vitamin D (kadar kalsidiol) merupakan salah satu faktor risiko terjadinya keganasan tiroid. Rasio netrofil limfosit (RNL) mencerminkan keseimbangan antara respon inflamasi protumor dan respon imun antitumor. Penelitian ini bertujuan untuk mengevaluasi hubungan antara kadar 25-hydroxyvitamin D serum dan RNL dengan keganasan nodul tiroid. Jenis penelitian ialah analitik observasional dengan desain potong lintang. Sampel penelitian ialah pasein dengan nodul tiroid yang dirawat di RSUP Prof. Dr. R. D. Kandou Hospital, Manado, sejak Agustus 2022 s/d Maret 2023. Hasil penelitian mendapatkan 46 pasien dengan keganasan tiroid yang memenuhi kriteria. Karakteristik sampel tebanyak ialah jenis kelamin perempuan (82,6%), rerata usia (50,2±14,74 tahun), status hormon tiroid normal (82,6%), rerata kadar 25-hydroxyvitamin D 32,25 ng/mL, rerata RNL 5, dan jenis keganasan karsinoma papiler (43,48%). Uji analisis Spearman menunjukkan keganasan tiroid secara bermakna berhubungan dengan kadar kalsidiol (r=-0,501, p=0), dan RNL (r=0,376, p=0,01). Simpulan penelitian ini ialah kadar 25-hydroxyvitamin D serum dan RNL dapat digunakan sebagai indikator untuk memrediksi keganasan nodul tiroid.

Kata Kunci: keganasan tiroid; 25-hydroxyvitamin D; rasio netrofil-limfosit

Author Biographies

Bryan D. Bogar, Universitas Sam Ratulangi

Program Pendidikan Dokter Spesialis Bagian Ilmu Bedah Fakultas Kedokteran Universitas Sam Ratulangi, Manado, Indonesia

Nico Lumintang, Universitas Sam Ratulangi

Bagian Ilmu Bedah Fakultas Kedokteran Universitas Sam Ratulangi - RSUP Prof. Dr. R. D. Kandou, Manado, Indonesia

Sherly Tandililing, Universitas Sam Ratulangi

Bagian Ilmu Bedah Fakultas Kedokteran Universitas Sam Ratulangi - RSUP Prof. Dr. R. D. Kandou, Manado, Indonesia

Windy M. Wariki, Universitas Sam Ratulangi

Bagian Ilmu Kedokteran Komunitas Fakultas Kedokteran Universitas Sam Ratulangi, Manado, Indonesia

References

Global Burden of Disease Cancer Collaboration, Fitzmaureice C, Abate D, Abbasi N, Abbastabar H, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with dis ability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study. JAMA Oncol. 2019;5(12):1749-68. Doi: 10.1001/jamaoncol. 2019.2996

World Health Organization. Number of new cases in 2020, both sexes, all ages. The Global Cancer Observatory. Cureus. 2020;11(2):e4127.

World Health Organization. Indonesia cancer. The Global Cancer Observatory. 2018. p1-2.

Haugen BR. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: what is new and what has changed? Cancer. 2017;123(3):372-81. Doi: 10.1002/cncr.30360

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov NJ, 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. Doi: 10.1089/thy.2015.0020.

Shah J. Thyroid carcinoma: epidemiology, histology, and diagnosis. Clin Adv Hematol Oncol. 2015;13(4 Suppl 4):3-6. Available from: https:// pubmed.ncbi.nlm.nih.gov/26430868/

Stepien T, Krupinski R, Sopinski J, Kuzdak K, Komorowski J, et al. Decreased 1-25 dihydroxy vitamin D3 concentration in peripheral blood serum of patients with thyroid cancer. Arch Med Res. 2010;41(3):190-4. Doi: 10.1016/j.arcmed.2010.04.004

Campbell M, Trump DL. Vitamin D receptor signaling and cancer. Endocrinol Metab Clin North Am. 2017;46(4):1009-38. Doi: 10.1016/j.ecl.2017.07.007

Roskies M, Dolev Y, Caglar D, Hier MP, Mlynarek A, Majdan A, et al. Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer. J Otolaryngol Head Neck Surg. 2012;41(3):160-3. Available from: https:// pubmed.ncbi.nlm.nih.gov/22762696/

Kim JR, Kim BH, Kim SM, Oh MY, Kim WJ, Jeon YK, et al. Low sefolikrum 25 hydroxyvitamin D is associated with poor clinicopathologic characteristics in female patients with papillary thyroid cancer. Thyroid. 2014;24(11):1618-24. Doi: 10.1089/thy.2014.0090

Suzuki S, Takenoshita S, Furukawa H, Tsuchiya A. Antineoplastic activity of l,25(OH)2D3 and its analogue 22-oxacalcitriol against human anaplastic thyroid carcinoma cell lines in vitro. Int J Mol Med. 1999;4(6):611-4. Doi: 10.3892/ijmm.4.6.611

Deeb KK, Trump TL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7(9):684-700. Doi: 10.1038/nrc2196

Dutta D, Sharma1 M, Aggarwal S, Mohindra R, Bhattacharya S, Kalra S. Vitamin D, thyroid autoimmunity and cancer: an interplay of different factors. Indian J Endocrinol Metab. 2019;23(5):507-13. Doi: 10.4103/ijem.IJEM_526_19

Zhao J, Wang H, Zhang Z, Zhou X, Yao J, Zhang R, et al. Vitamin D deficiency as a risk factor for thyroid cancer: a meta-analysis of case-control studies. The end-to-end journal. Nutrition. 2019:57:5-11. Doi: 10.1016/j.nut.2018.04.015

Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96(2):252-61. Doi: 10.2105/AJPH.2004.045260

Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014;14(5):342-57. Doi: 10.1038/nrc3691

Tabatabaeizadeh SA, Avan A, Bahrami A, Khodashenas E, Esmaeili H, Ferns GA, et al. High-dose supplementation of vitamin D affects measures of systemic inflammation: reductions in high-sensitivity C-reactive protein level and neutrophil to lymphocyte ratio (NLR) distribution. J Cell Biochem. 2017;118(12):4317-22. Doi: 10.1002/jcb.26084

Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014 May 29:7:69-87. doi: 10.2147/JIR.S63898

Akbas EM, Gungor A, Ozcicek A, Akbas N, Askin S, Polat M. Vitamin D and inflammation: evaluation with neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Arch Med Sci. 2016;12(4):721-7. Doi: 10.5114/aoms.2015.50625

Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jailon S. Tumor associated macrophages and neutrophils in cancer. Immunobiology. 2013;218(11):1402-10. Doi: 10.1016/j.imbio.2013.06.003

Ma SJ, Yu H, Khan M, Gill J, Santhosh S, Chatterjee U, et al. Evaluation of optimal threshold of neutrophil-lymphocyte ratio and its association with survival outcomes among patient with head and neck cancer. JAMA Network Open. 2022;5(4):e227567. Doi: 10.1001/jamanetworkopen.2022.7567

Yaylacı S, Tosun O, Sahin O, Genc AB, Aydin E, Demiral G, et al. Lack of variation in inflammatory hematological parameters between benign nodular goiter and papillary thyroid cancer. Asian Pac J Cancer Prev. 2016;17(4):2321-3. Doi: 10.7314/apjcp.2016.17.4.2321

Liu W, Zhang L, Xu H-J, Li Y, Hu C-M, Yang JY, et al. The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis. Int J Mol Sci. 2018;19(9):2736. doi: 10.3390/ijms19092736

Bartlett EK, Flynn JR, Panageas KS, Ferraro RA, Sta Cruz JM, Postow MA, et al. High neutrophil to lymphocyte ratio (NLR) is associated with treatment failure and death in melanoma patients treated with PD-1 inhibitor monotherapy. Cancer. 2020;126(1):76-85. Doi: 10.1002/cncr.32506

Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752-7. Doi: 10.4065/mcp.2010.0138

Hu MJ, Zhang Q, Liang L, Wang S-Y, Zheng X-C, Zhou M-M, et al. Association between vitamin D deficiency and risk of thyroid cancer: a case-control study and a meta-analysis. J Endocrinol Invest. 2018;41(10):1199-210. Doi: 10.1007/s40618-018-0853-9

Zabel M, Flig K, Gębarowska E, Zasada JS. The effect of calcitriol and its analogues on proliferation and hormone expression in cultured cells of thyroid medullary carcinomas. Folia Morphol. 2003;62(4):463-5. Available from: https://europepmc.org/article/MED/14655142

Balla B, Tobias B, Kosa JP, Podani J, Horvath P, Nagy Z, et al. Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer. J Endocrinol Invest. 2015 Mar;38(3):313-21. Doi: 10.1007/s40618-014-0165-7

Laney N, Meza J, Lyden E, Erickson J, Treude K, Goldner W. The prevalence of vitamin D deficiency is similar between thyroid nodule and thyroid cancer patients. International Journal of Endocrinology. 2009:2010:805716. Available from: https://doi.org/10.1155/2010/805716

Jonklaas J, Danielsen M, Wang H. A pilot study of serum selenium, vitamin D, and thyrotropin concentrations in patients with thyroid cancer. Thyroid. 2013;23(9):1079-86. Doi: 10.1089/thy.2012.0548

Ahn HY, Chung YJ, Park K-Y, Cho BY. Serum 25-hydroxyvitamin D level does not affect the aggressiveness and prognosis of papillary thyroid cancer. Thyroid. 2016;26(3):429-33. Doi: 10.1089/thy.2015.0516

Warakomski J, Romuk E, Jarząb B, Krajewska J, Siemińska L. Concentrations of selected adipokines, interleukin-6, and vitamin D in patients with papillary thyroid carcinoma in respect to thyroid cancer stages. Int J Endocrinol. 2018:2018:4921803. Doi: 10.1155/2018/4921803

Kuang J, Jin Z, Chen L, Zhao Q, Huang H, Liu Z, et al. Serum 25-hydroxyvitamin D level is unreliable as a risk factor and prognostic marker in papillary thyroid cancer. Ann Transl Med. 2022;10(4):193. Doi: 10.21037/atm-22-10.

Feng J, Wang Y,Shan G, Gao L.Clinical and prognostic value of neutrophil-lymphocyte ratio for patients with thyroid cancer. Medicine. Cina. 2020.p1-8.

Cheong TY, Hong DSJung K-W, So YK. The diagnostic predictive value of neutrophil-to-lymphocyte ratio in thyroid cancer adjusted for tumor size. Plos One. 2021;16(5):e0251446. Doi: 10.1371/ journal.pone.0251446

Kocer D, Karakukcu C, Karaman H, Gokay F, Bayram F. May the neutrophil/lymphocyte ratio be a predictor in the differentiation of different thyroid disorders? Asian Pac J Cancer Prev. 2015;16(9): 3875-9. Doi: 7314/apjcp.2015.16.9.3875

Riguetto CM, Barreto IS, Maia FFR, da Assumpção LVM, Zantut-Wittmann DEZ. Usefulness of pre-thyroidectomy neutrophil–lymphocyte, platelet–lymphocyte, and monocyte–lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer. Clinics (Sao Paulo). 2021:76:e3022. Doi: 10.6061/clinics/2021/e3022

Park JY, Park J, Shin J-H, Oh J-L, Jung H-A, Chung M-K, et al. Prognostic value of the neutrophil-to-lymphocyte ratio before and after radiotherapy for anaplastic thyroid carcinoma. Cancers (Basel). 2021;13(8):1913. Doi: 10.3390/cancers13081913

Downloads

Published

2024-02-19

How to Cite

Bogar, B. D., Lumintang, N., Tandililing, S., & Wariki, W. M. (2024). Korelasi antara Kadar Kalsidiol (25-Oh) dan Rasio Netrofil-Limfosit dengan Keganasan Nodul Tiroid. E-CliniC, 12(2), 205–212. https://doi.org/10.35790/ecl.v12i2.48492

Issue

Section

Articles