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Diagnostic value of microRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples

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Tumor Biology

Abstract

Many studies have suggested that microRNAs (miRNAs) might serve as novel diagnostic indicators of thyroid cancer (TC). However, inconsistent results have also been reported. This meta-analysis was conducted to assess the diagnostic value of miRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples. A systematic literature search for relevant literature published up to April 5, 2014 was conducted in PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM) databases. Data from different studies were pooled to estimate the summary sensitivity (SEN), specificity (SPE), positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR), using the random-effect model. Summary receiver operator characteristic curves (SROCs) were plotted and areas under the SROC curve (AUC) were calculated to evaluate the overall test performance. Between-study heterogeneity was tested using the Q tests and the I 2 statistics. Potential sources of heterogeneity were analyzed through subgroup analyses and meta-regression. Deeks’ funnel plot asymmetry test was performed to evaluate publication bias. All analyses were performed using STATA 12.0 software. Eighteen studies from 7 articles, including 543 patients with malignant thyroid nodules (n = 266) and benign ones (n = 277), were included in this meta-analysis. The pooled SEN was 0.77 (95 % CI: 0.70–0.83), SPN was 0.75 (95 % CI: 0.68–0.81), PLR was 3.1 (95 % CI: 2.4–4.0), NLR was 0.30 (95 % CI: 0.23–0.39), DOR was 10 (95 % CI: 7–16), and AUC was 0.83 (95 %CI: 0.79–0.86). Subgroup analyses indicated that multiple miRNAs assays showed a higher diagnostic accuracy than single miRNA assays. In conclusion, this meta-analysis suggests that miRNAs analysis can significantly improve diagnostic accuracy for differentiating malignant thyroid nodules from benign indeterminate ones on fine-needle aspiration (FNA) samples. With further confirmation, multiple miRNAs assays may play a critical role as a complement to fine-needle aspiration biopsy (FNAB).

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References

  1. Sipos JA, Mazzaferri EL. Thyroid cancer epidemiology and prognostic variables. Clin Oncol (R Coll Radiol). 2010;22:395–404.

    Article  CAS  Google Scholar 

  2. Cognetti DM, Pribitkin EA, Keane WM. Management of the neck in differentiated thyroid cancer. Surg Oncol Clin N Am. 2008;17:157–73.

    Article  PubMed  Google Scholar 

  3. Weir HK, Thun MJ, Hankey BF, Ries LA, Howe HL, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst. 2003;95:1276–99.

    Article  PubMed  Google Scholar 

  4. Gharib H. Changing trends in thyroid practice: understanding nodular thyroid disease. Endocr Pract. 2004;10:31–9.

    Article  PubMed  Google Scholar 

  5. Dean DS, Gharib H. Epidemiology of thyroid nodules. Best Pract Res Clin Endocrinol Metab. 2008;22:901–11.

    Article  PubMed  Google Scholar 

  6. Gharib H, Papini E, Valcavi R, Baskin HJ, Crescenzi A, Dottorini ME, et al. American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 2006;12:63–102.

    Article  PubMed  Google Scholar 

  7. Kato MA, Fahey 3rd TJ. Molecular markers in thyroid cancer diagnostics. Surg Clin N Am. 2009;89:1139–55.

    Article  PubMed  Google Scholar 

  8. Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011;21:243–51.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Mehanna HM, Jain A, Morton RP, Watkinson J, Shaha A. Investigating the thyroid nodule. BMJ. 2009;338:b733.

    Article  CAS  PubMed  Google Scholar 

  10. Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocrinol Relat Cancer. 2006;13:497–508.

    Article  CAS  Google Scholar 

  11. Weber F, Teresi RE, Broelsch CE, Frilling A, Eng C. A limited set of human microRNA is deregulated in follicular thyroid carcinoma. J Clin Endocrinol Metab. 2006;91:3584–91.

    Article  CAS  PubMed  Google Scholar 

  12. Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, et al. Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 2007;26:7590–5.

    Article  CAS  PubMed  Google Scholar 

  13. Martinez I, Dimaio D. B-Myb, cancer, senescence, and microRNAs. Cancer Res. 2011;71:5370–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Subramanyam D, Blelloch R. From microRNAs to targets: pathway discovery in cell fate transitions. Curr Opin Genet Dev. 2011;21:498–503.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Wilmott JS, Zhang XD, Hersey P, Scolyer RA. The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers. Pathology. 2011;43:657–71.

    CAS  PubMed  Google Scholar 

  16. Sheu SY, Grabellus F, Schwertheim S, Worm K, Broecker-Preuss M, Schmid KW. Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours. Br J Cancer. 2010;102:376–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Shen R, Liyanarachchi S, Li W, Wakely Jr PE, Saji M, Huang J, et al. MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia of undetermined significance" cases. Thyroid. 2012;22:9–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Keutgen XM, Filicori F, Crowley MJ, Wang Y, Scognamiglio T, Hoda R, et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012;18:2032–8.

    Article  CAS  PubMed  Google Scholar 

  19. Mazeh H, Levy Y, Mizrahi I, Appelbaum L, Ilyayev N, Halle D, et al. Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy. J Surg Res. 2013;180:216–21.

    Article  CAS  PubMed  Google Scholar 

  20. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.

    Article  PubMed  Google Scholar 

  21. Mitchell AJ, Vaze A, Rao S. Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009;374:609–19.

    Article  PubMed  Google Scholar 

  22. Harbord RM, Deeks JJ, Egger M, Whiting P, Sterne JA. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2007;8:239–51.

    Article  PubMed  Google Scholar 

  23. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess. 2005;9:1–113. iii.

    Article  CAS  Google Scholar 

  25. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58:882–93.

    Article  PubMed  Google Scholar 

  26. Kitano M, Rahbari R, Patterson EE, Xiong Y, Prasad NB, Wang Y, et al. Expression profiling of difficult-to-diagnose thyroid histologic subtypes shows distinct expression profiles and identify candidate diagnostic microRNAs. Ann Surg Oncol. 2011;18:3443–52.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Mazeh H, Mizrahi I, Halle D, Ilyayev N, Stojadinovic A, Trink B, et al. Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples. Thyroid. 2011;21:111–8.

    Article  CAS  PubMed  Google Scholar 

  28. Kitano M, Rahbari R, Patterson EE, Steinberg SM, Prasad NB, Wang Y, et al. Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples. Thyroid. 2012;22:285–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Vriens MR, Weng J, Suh I, Huynh N, Guerrero MA, Shen WT, et al. MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer. Cancer. 2012;118:3426–32.

    Article  CAS  PubMed  Google Scholar 

  30. Finley BL, Pierce JS, Paustenbach DJ, Scott LL, Lievense L, Scott PK, et al. Malignant pleural mesothelioma in US automotive mechanics: reported vs expected number of cases from 1975 to 2007. Regul Toxicol Pharmacol. 2012;64:104–16.

    Article  PubMed  Google Scholar 

  31. Khan SY, Tariq MA, Perrott JP, Brumbaugh CD, Kim HJ, Shabbir MI, et al. Distinctive microRNA expression signatures in proton-irradiated mice. Mol Cell Biochem. 2013;382:225–35.

    Article  CAS  PubMed  Google Scholar 

  32. Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara JS, Ip JC, et al. MicroRNA-222 and microRNA-146b are tissue and circulating biomarkers of recurrent papillary thyroid cancer. Cancer. 2013;119:4358–65.

    Article  CAS  PubMed  Google Scholar 

  33. Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009;94:2092–8.

    Article  CAS  PubMed  Google Scholar 

  34. Eszlinger M, Paschke R. Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Mol Cell Endocrinol. 2010;322:29–37.

    Article  CAS  PubMed  Google Scholar 

  35. Mazzanti C, Zeiger MA, Costouros NG, Umbricht C, Westra WH, Smith D, et al. Using gene expression profiling to differentiate benign versus malignant thyroid tumors. Cancer Res. 2004;64:2898–903.

    Article  CAS  PubMed  Google Scholar 

  36. Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Ann Surg. 2005;242:353–61. discussion 61–3.

    PubMed Central  PubMed  Google Scholar 

  37. Tetzlaff MT, Liu A, Xu X, Master SR, Baldwin DA, Tobias JW, et al. Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues. Endocr Pathol. 2007;18:163–73.

    Article  CAS  PubMed  Google Scholar 

  38. Chen YT, Kitabayashi N, Zhou XK, Fahey 3rd TJ, Scognamiglio T. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod Pathol. 2008;21:1139–46.

    Article  CAS  PubMed  Google Scholar 

  39. Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93:1600–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Hummel R, Hussey DJ, Haier J. MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer. 2010;46:298–311.

    Article  CAS  PubMed  Google Scholar 

  41. Cho WC. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer. 2007;6:60.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Zhang B, Pan X, Cobb GP, Anderson TA. MicroRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.

    Article  CAS  PubMed  Google Scholar 

  43. Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med. 2009;60:167–79.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the grants from the National Natural Science Foundation of China (grant number: 81302374 and 81241084), Beijing Natural Science Foundation (grant numbers: 7121005 and 5122016), and Beijing Nova Program (grant number: xx2013043), Capital Development Fund for medical research (grant numbers: 2011-2005-06), Scientific Research Project of Beijing Educational Committee (grant numbers: KZ201310025025, PXM_2013_014226_07_000060,20121002502).

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  1. Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Key Laboratory of Otolaryngology Head and Neck Surgery, Capital Medical University, No.1 Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, China

    Yang Zhang, Qi Zhong, Xiaohong Chen, Jugao Fang & Zhigang Huang

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Correspondence to Zhigang Huang.

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Zhang, Y., Zhong, Q., Chen, X. et al. Diagnostic value of microRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples. Tumor Biol. 35, 9343–9353 (2014). https://doi.org/10.1007/s13277-014-2209-1

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