Multimedialna platforma wiedzy medycznej Internetowa Księgarnia Medyczna Kalendarium Konferencji
Endokrynologia Polska
MENU
Shortcuts Submit an article Author Guidelines Polish Society of Endocrinology Reviewers 2023 Redeem voucher

open access

Vol 72, No 2 (2021)
Review paper
Submitted: 2020-11-29
Accepted: 2021-01-08
Published online: 2021-04-30
View PDF Download PDF file Supp./Additional Files [1]
Get Citation

Dysregulation of microRNAs as the risk factor of lymph node metastasis in papillary thyroid carcinoma: systematic review

Romena Laukiene1, Valentinas Jakubkevicius2, Laima Ambrozaityte1, Loreta Cimbalistiene1, Algirdas Utkus1
DOI: 10.5603/EP.a2021.0010
·
Pubmed: 33970479
·
Endokrynol Pol 2021;72(2):145-152.
Affiliations
  1. Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
  2. Faculty of Medicine, Vilnius University, Vilnius, Lithuania

open access

Vol 72, No 2 (2021)
Review Article
Submitted: 2020-11-29
Accepted: 2021-01-08
Published online: 2021-04-30

Abstract

Papillary thyroid carcinoma (PTC) has an excellent prognosis with a relatively low mortality rate, but a small portion of PTC patients suffer from an aggressive form of the disease. In such cases early detection of lymph node metastasis (LNM) is as paramount as it is problematic. The routine use of central neck lymph node dissection is not recommended. New methods to detect LNM are needed. MicroRNAs are a potential biomarker for diagnosis and prognosis of PTC. In this review we summarise the current knowledge regarding dysregulated miRNAs and their association with LNM in PTS patients.

The PubMed and EBSCO databases were searched using terms for “microRNA”, “thyroid carcinoma”, and “prognosis” by using Boolean operators. Based on eligibility and exclusion criteria, articles were screened and reviewed in full, methodological data of included studies were extracted, and risk of bias analysis performed.

In total, 446 unique studies were extracted from the mentioned databases, and based on inclusion and exclusion criteria 27 studies were included in this review. Of them 17 analysed tissue microRNAs, 5 analysed circulating microRNAs, and 5 studies analysed both tissue and circulating samples. MiRNA-146B, miRNA-221, miRNA-222, miRNA-21, miRNA-204, miRNA-451, miRNA-199a-3p, and miRNA-30a-3p were dysregulated in at least 2 separate studies. A sizable portion of studies failed to show statistically significant differences in miRNA expression between LNM-positive and -negative patients. Different methodologies and disparities of patient populations could explain these discrepancies.\

This research supports the statement that specific up- and downregulated miRNAs are associated with LNM in PTC patients. However, the prognostic value of these miRNAs is limited. Additional targeted cohort studies are required to elucidate the role of miRNAs in defining individualised treatment strategies for thyroid cancer patients.

Abstract

Papillary thyroid carcinoma (PTC) has an excellent prognosis with a relatively low mortality rate, but a small portion of PTC patients suffer from an aggressive form of the disease. In such cases early detection of lymph node metastasis (LNM) is as paramount as it is problematic. The routine use of central neck lymph node dissection is not recommended. New methods to detect LNM are needed. MicroRNAs are a potential biomarker for diagnosis and prognosis of PTC. In this review we summarise the current knowledge regarding dysregulated miRNAs and their association with LNM in PTS patients.

The PubMed and EBSCO databases were searched using terms for “microRNA”, “thyroid carcinoma”, and “prognosis” by using Boolean operators. Based on eligibility and exclusion criteria, articles were screened and reviewed in full, methodological data of included studies were extracted, and risk of bias analysis performed.

In total, 446 unique studies were extracted from the mentioned databases, and based on inclusion and exclusion criteria 27 studies were included in this review. Of them 17 analysed tissue microRNAs, 5 analysed circulating microRNAs, and 5 studies analysed both tissue and circulating samples. MiRNA-146B, miRNA-221, miRNA-222, miRNA-21, miRNA-204, miRNA-451, miRNA-199a-3p, and miRNA-30a-3p were dysregulated in at least 2 separate studies. A sizable portion of studies failed to show statistically significant differences in miRNA expression between LNM-positive and -negative patients. Different methodologies and disparities of patient populations could explain these discrepancies.\

This research supports the statement that specific up- and downregulated miRNAs are associated with LNM in PTC patients. However, the prognostic value of these miRNAs is limited. Additional targeted cohort studies are required to elucidate the role of miRNAs in defining individualised treatment strategies for thyroid cancer patients.

Full Text:

View PDF Download PDF file Supp./Additional Files [1]
Get Citation

Keywords

thyroid neoplasms; microRNAs; lymphatic metastasis

Supp./Additional Files (1)
Supplementary File
Download
115KB
About this article
Title

Dysregulation of microRNAs as the risk factor of lymph node metastasis in papillary thyroid carcinoma: systematic review

Journal

Endokrynologia Polska

Issue

Vol 72, No 2 (2021)

Article type

Review paper

Pages

145-152

Published online

2021-04-30

Page views

1846

Article views/downloads

832

DOI

10.5603/EP.a2021.0010

Pubmed

33970479

Bibliographic record

Endokrynol Pol 2021;72(2):145-152.

Keywords

thyroid neoplasms
microRNAs
lymphatic metastasis

Authors

Romena Laukiene
Valentinas Jakubkevicius
Laima Ambrozaityte
Loreta Cimbalistiene
Algirdas Utkus

References (55)
  1. Pellegriti G, Frasca F, Regalbuto C, et al. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013; 2013: 965212.
    CrossRefPubMed
  2. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010; 127(12): 2893–2917.
    CrossRefPubMed
  3. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006; 295(18): 2164–2167.
    CrossRefPubMed
  4. Cho SW, Choi HS, Yeom GJ, et al. Long-term prognosis of differentiated thyroid cancer with lung metastasis in Korea and its prognostic factors. Thyroid. 2014; 24(2): 277–286.
    CrossRefPubMed
  5. Tao Y, Wang C, Li L, et al. Clinicopathological features for predicting central and lateral lymph node metastasis in papillary thyroid microcarcinoma: Analysis of 66 cases that underwent central and lateral lymph node dissection. Mol Clin Oncol. 2017; 6(1): 49–55.
    CrossRefPubMed
  6. Wada N, Duh QY, Sugino K, et al. Lymph Node Metastasis From 259 Papillary Thyroid Microcarcinomas. Ann Surg. 2003; 237(3): 399–407.
    CrossRefPubMed
  7. 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): 372–381.
    CrossRefPubMed
  8. Chen L, Wu YH, Lee CH, et al. Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma with Clinically Uninvolved Central Neck Lymph Nodes: A Systematic Review and Meta-analysis. World J Surg. 2018; 42(9): 2846–2857.
    CrossRefPubMed
  9. Tan W, Liu B, Qu S, et al. MicroRNAs and cancer: Key paradigms in molecular therapy. Oncol Lett. 2018; 15(3): 2735–2742.
    CrossRefPubMed
  10. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281–297.
    CrossRefPubMed
  11. Santiago K, Chen Wongworawat Y, Khan S. Differential MicroRNA-Signatures in Thyroid Cancer Subtypes. J Oncol. 2020; 2020: 2052396.
    CrossRefPubMed
  12. Ab Mutalib NS, Othman SN, Mohamad Yusof A, et al. Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis. PeerJ. 2016; 4: e2119.
    CrossRefPubMed
  13. Moher D, Liberati A, Tetzlaff J, et al. PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Med. 2009; 3(3): e123–e130.
    PubMed
  14. Whiting PF, Rutjes AWS, Westwood ME, et al. QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011; 155(8): 529–536.
    CrossRefPubMed
  15. Chou CK, Chen RF, Chou FF, et al. miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. Thyroid. 2010; 20(5): 489–494.
    CrossRefPubMed
  16. Shi C, Cao J, Shi T, et al. BRAF mutation, BRAF-activated long non-coding RNA and miR-9 expression in papillary thyroid carcinoma, and their association with clinicopathological features. World J Surg Oncol. 2020; 18(1): 145.
    CrossRefPubMed
  17. Yu S, Liu Y, Wang J, et al. Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2012; 97(6): 2084–2092.
    CrossRefPubMed
  18. Zhou YL, Liu C, Dai Xx, et al. Overexpression of miR-221 is associated with aggressive clinicopathologic characteristics and the BRAF mutation in papillary thyroid carcinomas. Med Oncol. 2012; 29(5): 3360–3366.
    CrossRefPubMed
  19. Sun Y, Yu S, Liu Y, et al. Expression of miRNAs in Papillary Thyroid Carcinomas Is Associated with BRAF Mutation and Clinicopathological Features in Chinese Patients. Int J Endocrinol. 2013; 2013: 128735.
    CrossRefPubMed
  20. Wang Z, Zhang H, He L, et al. Association between the expression of four upregulated miRNAs and extrathyroidal invasion in papillary thyroid carcinoma. Onco Targets Ther. 2013; 6: 281–287.
    CrossRefPubMed
  21. Wang Z, Zhang H, Zhang P, et al. Upregulation of miR-2861 and miR-451 expression in papillary thyroid carcinoma with lymph node metastasis. Med Oncol. 2013; 30(2): 577.
    CrossRefPubMed
  22. Peng Y, Li C, Luo DC, et al. Expression profile and clinical significance of microRNAs in papillary thyroid carcinoma. Molecules. 2014; 19(8): 11586–11599.
    CrossRefPubMed
  23. Lee YSe, Lim YS, Lee JC, et al. Differential expression levels of plasma-derived miR-146b and miR-155 in papillary thyroid cancer. Oral Oncol. 2015; 51(1): 77–83.
    CrossRefPubMed
  24. Acibucu F, Dökmetaş HS, Tutar Y, et al. Correlations between the expression levels of micro-RNA146b, 221, 222 and p27Kip1 protein mRNA and the clinicopathologic parameters in papillary thyroid cancers. Exp Clin Endocrinol Diabetes. 2014; 122(3): 137–143.
    CrossRefPubMed
  25. Sun M, Fang S, Li W, et al. Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma. Cancer Biomark. 2015; 15(1): 33–40.
    CrossRefPubMed
  26. Han PA, Kim Hs, Cho S, et al. Association of BRAF V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers. Thyroid. 2016; 26(4): 532–542.
    CrossRefPubMed
  27. Hu J, Li C, Liu C, et al. Expressions of miRNAs in papillary thyroid carcinoma and their associations with the clinical characteristics of PTC. Cancer Biomark. 2017; 18(1): 87–94.
    CrossRefPubMed
  28. Liu Na, Zhou Qi, Qi YH, et al. Effects of long non-coding RNA H19 and microRNA let7a expression on thyroid cancer prognosis. Exp Mol Pathol. 2017; 103(1): 71–77.
    CrossRefPubMed
  29. Huang T, Yi D, Xu L, et al. Downregulation of miR-381 is associated with poor prognosis in papillary thyroid carcinoma. Int J Clin Exp Pathol. 2017; 10(12): 11610–11616.
    PubMed
  30. Ren G, Li H, He X, et al. Downregulation of serum miR-26a predicts poor clinical outcome of papillary thyroid carcinoma. Int J Clin Exp Pathol. 2017; 10(8): 9042–9047.
    PubMed
  31. Liu C, Xing M, Wang L, et al. miR-199a-3p downregulation in thyroid tissues is associated with invasion and metastasis of papillary thyroid carcinoma. Br J Biomed Sci. 2017; 74(2): 90–94.
    CrossRefPubMed
  32. Zhang M, Wu W, Gao M, et al. MicroRNA-451 as a prognostic marker for diagnosis and lymph node metastasis of papillary thyroid carcinoma. Cancer Biomark. 2017; 19(4): 437–445.
    CrossRefPubMed
  33. Todorović L, Stanojević B, Mandušić V, et al. Expression of VHL tumor suppressor mRNA and miR-92a in papillary thyroid carcinoma and their correlation with clinical and pathological parameters. Med Oncol. 2018; 35(2): 17.
    CrossRefPubMed
  34. Yang F, Zhang H, Leng X, et al. miR-146b measurement in FNA to distinguish papillary thyroid cancer from benign thyroid masses. Br J Biomed Sci. 2018; 75(1): 43–45.
    CrossRefPubMed
  35. Todorović L, Mandušić V, Tadić BV, et al. Altered expression of microRNA-30a-3p in papillary thyroid cancer and its association with clinicopathological characteristics. Arch Biol Sci. 2020; 72: 31–36.
    CrossRef
  36. Xiang D, Tian B, Yang T, et al. miR-222 expression is correlated with the ATA risk stratifications in papillary thyroid carcinomas. Medicine (Baltimore). 2019; 98(25): e16050.
    CrossRefPubMed
  37. Yao XG, Tan Q, Liu PP, et al. Tissue microRNA-182 expression level and its potential prognostic value for papillary thyroid carcinoma. Int J Clin Exp Pathol. 2019; 12(8): 3128–3133.
    PubMed
  38. Jiang Ke, Li G, Chen W, et al. Plasma Exosomal miR-146b-5p and miR-222-3p are Potential Biomarkers for Lymph Node Metastasis in Papillary Thyroid Carcinomas. Onco Targets Ther. 2020; 13: 1311–1319.
    CrossRefPubMed
  39. Dai D, Tan Y, Guo L, et al. Identification of exosomal miRNA biomarkers for diagnosis of papillary thyroid cancer by small RNA sequencing. Eur J Endocrinol. 2020; 182(1): 111–121.
    CrossRefPubMed
  40. Pamedytyte D, Simanaviciene V, Dauksiene D, et al. Association of MicroRNA Expression and BRAF Mutation with Recurrence of Thyroid Cancer. Biomolecules. 2020; 10(4).
    CrossRefPubMed
  41. Liu Y, Li L, Liu Z, et al. Plasma miR-323 as a Biomarker for Screening Papillary Thyroid Cancer From Healthy Controls. Front Med (Lausanne). 2020; 7: 122.
    CrossRefPubMed
  42. Ludvíková M, Kalfeřt D, Kholová I. Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration. Acta Cytol. 2015; 59(6): 435–444.
    CrossRefPubMed
  43. Fuziwara CS, Kimura ET. MicroRNAs in thyroid development, function and tumorigenesis. Mol Cell Endocrinol. 2017; 456: 44–50.
    CrossRefPubMed
  44. Qiu Z, Li H, Wang J, et al. miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma. Oncol Rep. 2017; 38(5): 2735–2740.
    CrossRefPubMed
  45. Lima CR, Geraldo MV, Fuziwara CS, et al. MiRNA-146b-5p upregulates migration and invasion of different Papillary Thyroid Carcinoma cells. BMC Cancer. 2016; 16: 108.
    CrossRefPubMed
  46. Chou CK, Yang KD, Chou FF, et al. Prognostic implications of miR-146b expression and its functional role in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2013; 98(2): E196–E205.
    CrossRefPubMed
  47. Chen Xi, Ba Yi, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008; 18(10): 997–1006.
    CrossRefPubMed
  48. Khordadmehr M, Jigari-Asl F, Ezzati H, et al. A comprehensive review on miR-451: A promising cancer biomarker with therapeutic potential. J Cell Physiol. 2019; 234(12): 21716–21731.
    CrossRefPubMed
  49. Goto A, Tanaka M, Yoshida M, et al. The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases. PLoS One. 2017; 12(7): e0181270.
    CrossRefPubMed
  50. Liu X, Zhang A, Xiang J, et al. miR-451 acts as a suppressor of angiogenesis in hepatocellular carcinoma by targeting the IL-6R-STAT3 pathway. Oncol Rep. 2016; 36(3): 1385–1392.
    CrossRefPubMed
  51. Bai H, Wu S. miR-451: A Novel Biomarker and Potential Therapeutic Target for Cancer. Onco Targets Ther. 2019; 12: 11069–11082.
    CrossRefPubMed
  52. Deng Y, Zhao F, Hui L, et al. Suppressing miR-199a-3p by promoter methylation contributes to tumor aggressiveness and cisplatin resistance of ovarian cancer through promoting DDR1 expression. J Ovarian Res. 2017; 10(1): 50.
    CrossRefPubMed
  53. Han Ye, Kuang Y, Xue X, et al. NLK, a novel target of miR-199a-3p, functions as a tumor suppressor in colorectal cancer. Biomed Pharmacother. 2014; 68(5): 497–505.
    CrossRefPubMed
  54. Ghosh A, Dasgupta D, Ghosh A, et al. MiRNA199a-3p suppresses tumor growth, migration, invasion and angiogenesis in hepatocellular carcinoma by targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2. Cell Death Dis. 2017; 8(3): e2706.
    CrossRefPubMed
  55. Mutalib NSAb, Yusof AM, Mokhtar NM, et al. MicroRNAs and Lymph Node Metastasis in Papillary Thyroid Cancers. Asian Pac J Cancer Prev. 2016; 17(1): 25–35.
    CrossRefPubMed

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.

Via MedicaWydawcą jest  VM Media Group sp. z o.o., Grupa Via Medica, ul. Świętokrzyska 73, 80–180 Gdańsk

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