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MicroRNA Signature Distinguishes the Degree of Aggressiveness of Papillary Thyroid Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Papillary thyroid carcinoma (PTC) has relatively indolent behavior, although some tumors recur and disseminate to distant sites. The aggressive biological behavior of PTC is difficult to predict. MicroRNAs (miRNAs) are dysregulated in various tumors types, and some of them serve as markers of poor prognosis. In this study, we evaluated miRNA expression as a marker of more aggressive behavior in PTC.

Methods

miRNA array was used to identify a subset of differentially expressed miRNAs between aggressive and nonaggressive PTC. These miRNAs were further validated by real-time RT-PCR in a cohort of 17 PTC with local tumor recurrence or distant metastases and 15 PTC with no extrathyroidal dissemination and correlated with BRAF, RAS, and RET/PTC mutations and MET expression.

Results

The miRNA array identified miR-146b, miR-221, miR-222, miR-155, miR-31 upregulation and miR-1, miR-34b, miR-130b, miR-138 downregulation in aggressive compared with nonaggressive PTC. Significant miRNA deregulation was confirmed in the validation cohort, with upregulation of miR-146b and miR-222 and downregulation of miR-34b and miR-130b seen in aggressive PTC. Among BRAF-positive tumors, miR-146b showed strong association with aggressive PTC. MET was identified as a potential target gene for 2 downregulated miRNAs (miR-34b and miR-1), and significantly higher level of MET expression was observed in aggressive PTC.

Conclusions

We demonstrate that miR-146b, miR-222, miR-34b, miR-130b are differentially expressed in aggressive compared with nonaggressive PTC. Among BRAF-positive tumors, overexpression of miR-146b was associated with aggressive behavior, suggesting that it may further refine the prognostic importance of BRAF.

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Acknowledgement

This work was supported in part by the National Institute of Health grant R01 CA88041 to Y.E. N.

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Authors and Affiliations

  1. Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Linwah Yip MD, Michaele J. Armstrong PhD & Sally E. Carty MD

  2. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Lindsey Kelly BS, Yuri E. Nikiforov MD, PhD & Marina N. Nikiforova MD

  3. University of Pittsburgh Cancer Institute Biostatistics Facility, Pittsburgh, PA, USA

    Yongli Shuai MS

Authors
  1. Linwah Yip MD
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  2. Lindsey Kelly BS
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  3. Yongli Shuai MS
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  5. Yuri E. Nikiforov MD, PhD
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  6. Sally E. Carty MD
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  7. Marina N. Nikiforova MD
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Correspondence to Marina N. Nikiforova MD.

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Yip, L., Kelly, L., Shuai, Y. et al. MicroRNA Signature Distinguishes the Degree of Aggressiveness of Papillary Thyroid Carcinoma. Ann Surg Oncol 18, 2035–2041 (2011). https://doi.org/10.1245/s10434-011-1733-0

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  • DOI: https://doi.org/10.1245/s10434-011-1733-0

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