Genetic markers associated with resistance to radioiodine therapy in thyroid cancer patients: Prospective cohort study
- 作者: Denisenko N.1,2, Shuev G.2, Mukhamadiev R.2, Perfilieva O.2, Kazakov R.2, Kachanova A.2, Milyutina O.2, Konenkova O.2, Ryzhkin S.2, Ivashchenko D.1,2, Bure I.1,2, Kirienko S.2, Zhmaeva E.2, Mirzaev K.1,2, Ametov A.2, Poddubnaya I.2, Sychev D.2
-
隶属关系:
- Centre for Personalized Medicine
- Russian Medical Academy of Continuous Professional Education
- 期: 卷 24, 编号 3 (2022)
- 页面: 345-350
- 栏目: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/110799
- DOI: https://doi.org/10.26442/18151434.2022.3.201867
- ID: 110799
如何引用文章
全文:
详细
Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients.
Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients.
Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.5±15.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan™ kits.
Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p>0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04.
Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to 131I therapy.
关键词
作者简介
Natalia Denisenko
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
编辑信件的主要联系方式.
Email: natalypilipenko3990@gmail.com
ORCID iD: 0000-0003-3278-5941
SPIN 代码: 5883-6249
Cand. Sci. (Med.)
俄罗斯联邦, Saint Petersburg; MoscowGrigorij Shuev
Russian Medical Academy of Continuous Professional Education
Email: shuevgrigorii@gmail.com
ORCID iD: 0000-0002-5031-0088
SPIN 代码: 4172-1330
Res. Assist.
俄罗斯联邦, MoscowReis Mukhamadiev
Russian Medical Academy of Continuous Professional Education
Email: rmuhamadiev@gmail.com
ORCID iD: 0000-0002-8052-4984
Resident
俄罗斯联邦, MoscowOksana Perfilieva
Russian Medical Academy of Continuous Professional Education
Email: operfileva@mail.ru
SPIN 代码: 5453-5031
Cand. Sci. (Med.)
俄罗斯联邦, MoscowRuslan Kazakov
Russian Medical Academy of Continuous Professional Education
Email: rustic100@rambler.ru
ORCID iD: 0000-0003-0802-4229
SPIN 代码: 8751-5090
Cand. Sci. (Biol.)
俄罗斯联邦, MoscowAnastasia Kachanova
Russian Medical Academy of Continuous Professional Education
Email: aakachanova@yandex.ru
ORCID iD: 0000-0003-3194-4410
SPIN 代码: 1214-8156
Res. Assist.
俄罗斯联邦, MoscowOlga Milyutina
Russian Medical Academy of Continuous Professional Education
Email: miliutina.olia2017@yandex.ru
ORCID iD: 0000-0002-6828-3831
Resident
俄罗斯联邦, MoscowOlga Konenkova
Russian Medical Academy of Continuous Professional Education
Email: konenkova.olia@yandex.ru
ORCID iD: 0000-0002-4789-2718
Resident
俄罗斯联邦, MoscowSergey Ryzhkin
Russian Medical Academy of Continuous Professional Education
Email: rsa777@inbox.ru
ORCID iD: 0000-0003-2595-353X
SPIN 代码: 5955-5712
D. Sci. (Med.), Assoc. Prof.
俄罗斯联邦, MoscowDmitriy Ivashchenko
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Email: dvi1991@yandex.ru
ORCID iD: 0000-0002-2295-7167
SPIN 代码: 9435-7794
D. Sci. (Med.)
俄罗斯联邦, Saint Petersburg; MoscowIrina Bure
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Email: bureira@mail.ru
ORCID iD: 0000-0003-2043-5848
SPIN 代码: 3212-7905
Cand. Sci. (Biol.)
俄罗斯联邦, Saint Petersburg; MoscowSergey Kirienko
Russian Medical Academy of Continuous Professional Education
Email: ii_po_klinica_rmapo@mail.ru
Department Рead
俄罗斯联邦, MoscowElena Zhmaeva
Russian Medical Academy of Continuous Professional Education
Email: zhem1504@mail.ru
Cand. Sci. (Med.)
俄罗斯联邦, MoscowKarin Mirzaev
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Email: karin05doc@yandex.ru
ORCID iD: 0000-0002-9307-4994
SPIN 代码: 8308-7599
D. Sci. (Med.)
俄罗斯联邦, Saint Petersburg; MoscowAlexander Ametov
Russian Medical Academy of Continuous Professional Education
Email: alexander.ametov@gmail.com
ORCID iD: 0000-0002-7936-7619
SPIN 代码: 9511-1413
D. Sci. (Med.), Prof.
俄罗斯联邦, MoscowIrina Poddubnaya
Russian Medical Academy of Continuous Professional Education
Email: poddubnaya_irina@inbox.ru
ORCID iD: 0000-0002-0995-1801
SPIN 代码: 1146-9889
D. Sci. (Med.), Prof., Acad. RAS
俄罗斯联邦, MoscowDmitry Sychev
Russian Medical Academy of Continuous Professional Education
Email: dmitry.alex.sychev@gmail.com
ORCID iD: 0000-0002-4496-3680
SPIN 代码: 4525-7556
D. Sci. (Med.), Prof., Acad. RAS
俄罗斯联邦, Moscow参考
- Van Nostrand D. The Benefits and Risks of I-131 Therapy in Patients with Well-Differentiated Thyroid Cancer. Thyroid. 2009;19(12):1381-91. doi: 10.1089/thy.2009.1611
- Клинические рекомендации «Дифференцированный рак щитовидной железы» (утв. Минздравом России, 2020 г.). Режим доступа: https://cr.minzdrav.gov.ru/recomend/329_1. Ссылка активна на 16.04.2022 [Clinical recommendations: differentiated thyroid cancer (approved by the Ministry of Health of Russia, 2020). Available at: https://cr.minzdrav.gov.ru/recomend/329_1. Accessed: 16.04.2022 (in Russian)].
- Jackson S, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461(7267):1071-8. doi: 10.1038/nature08467
- Yan M, Tang C, Ma Z, et al. DNA damage response in nephrotoxic and ischemic kidney injury. Toxicol Appl Pharmacol. 2016;313:104-108. doi: 10.1016/j.taap.2016.10.022
- Marechal A, Zou L. DNA Damage Sensing by the ATM and ATR Kinases. Cold Spring Harb Perspect Biol. 2013;5(9):a012716. doi: 10.1101/cshperspect.a012716
- Thomasova D, Mulay SR, Bruns H, Anders HJ. p53-Independent Roles of MDM2 in NF-κB Signaling: Implications for Cancer Therapy, Wound Healing, and Autoimmune Diseases. Neoplasia. 2012;14(12):1097-101. doi: 10.1593/neo.121534
- Boya P, Reggiori F, Codogno P. Emerging regulation and functions of autophagy. Nat Cell Biol. 2013;15(7):713-20. doi: 10.1038/ncb2788
- Katayama M, Kawaguchi T, Berger M, Pieper R. DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ. 2007;14(3):548-58. doi: 10.1038/sj.cdd.4402030
- Dyavaiah M, Rooney J, Chittur S, et al. Autophagy-Dependent Regulation of the DNA Damage Response Protein Ribonucleotide Reductase 1. Mol Cancer Res. 2011;9(4):462-75. doi: 10.1158/1541-7786.mcr-10-0473
- Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27-42.
- Sridhar S, Botbol Y, Macian F, Cuervo A. Autophagy and disease: always two sides to a problem. J Pathol. 2011;226(2):255-73. doi: 10.1002/path.3025
- Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333(1-2):169-74. doi: 10.1016/0014-5793(93)80398-e
- Lamb C, Yoshimori T, Tooze S. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14(12):759-74. doi: 10.1038/nrm3696
- Ishibashi K, Fujita N, Kanno E, et al. Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12–5-16L2 complex. Autophagy. 2011;7(12):1500-13. doi: 10.4161/auto.7.12.18025
- Tang J, Wang D, Shen Y, Xue F. ATG16L2 overexpression is associated with a good prognosis in colorectal cancer. J Gastrointest Oncol. 2021;12(5):2192-202. doi: 10.21037/jgo-21-495
- Zhou Q, Chen X, Chen Q, et al. A Four Autophagy-Related Gene-Based Prognostic Signature for Pancreatic Cancer. Crit Rev Eukaryot Gene Expr. 2021;31(4):89-100. doi: 10.1615/critreveukaryotgeneexpr.2021038733
- Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1856-83. doi: 10.1093/annonc/mdz400
- Kastan MB, Lim DS, Kim ST, Yang D. ATM--A Key Determinant of Multiple Cellular Responses to Irradiation. Acta Oncol. (Madr). 2001;40(6):686-8. doi: 10.1080/02841860152619089
- Hickson I, Zhao Y, Richardson CJ, et al. Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM. Cancer Res. 2004;64(24):9152-9. doi: 10.1158/0008-5472.CAN-04-2727
- Aggarwal BB, Sung B. NF-κB in Cancer: A Matter of Life and Death: Figure 1. Cancer Discov. 2011;1(6):469-71. doi: 10.1158/2159-8290.CD-11-0260
- Perkins ND. The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer. 2012;12(2):121-32. doi: 10.1038/nrc3204
- Wu Z, Shi Y, Tibbetts R, Miyamoto S. Molecular Linkage Between the Kinase ATM and NF-κB Signaling in Response to Genotoxic Stimuli. Science. 2006;311(5764):1141-6. doi: 10.1126/science.1121513
- Plantinga T, Petrulea M, Oosting M, et al. Association of NF-κB polymorphisms with clinical outcome of non-medullary thyroid carcinoma. Endocr Relat Cancer. 2017:307-18. doi: 10.1530/erc-17-0033
- Liu J, Tang X, Shi F, et al. Genetic polymorphism contributes to 131I radiotherapy-induced toxicities in patients with differentiated thyroid cancer. Pharmacogenomics. 2018;19(17):1335-44. doi: 10.2217/pgs-2018-0070
- Xie K, Liang C, Li Q, et al. Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival. Int J Cancer. 2016;139(7):1564-73. doi: 10.1002/ijc.30205
- Bai H, He Y, Lin Y, et al. Identification of a novel differentially methylated region adjacent to ATG16L2 in lung cancer cells using methyl-CpG binding domain protein-enriched genome sequencing. Genome. 2021;64(5):533-46. doi: 10.1139/gen-2020-0071
- Yang Z, Liu Z. Potentially functional variants of autophagy-related genes are associated with the efficacy and toxicity of radiotherapy in patients with nasopharyngeal carcinoma. Mol Genet Genomic Med. 2019;7(12):e1030. doi: 10.1002/mgg3.1030