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The miR-221/222 cluster, miR-10b and miR-92a are highly upregulated in metastatic minimally invasive follicular thyroid carcinoma.

Abstract
Minimally invasive follicular thyroid carcinoma (MI-FTC) is characterized by limited capsular and/or vascular invasion with good long-term outcomes. However, some cases of MI-FTC show a poor prognosis because of severe distant metastasis (i.e., metastatic MI-FTC). Nonetheless, no method has been established for predicting the prognosis of MI-FTC. This study was conducted to identify novel prognostic factors for metastatic MI-FTC by the use of microRNA (miRNA). Thirty-four patients with MI-FTC were categorized into two groups: the metastatic group, M(+) (n=12) and the non-metastatic group, M(-) (n=22). In the M(+) group, distant metastasis was recognized after the initial operation established the diagnosis of MI-FTC. In the M(-) group, no distant metastasis was recognized postoperatively for ≥ 10 years. Using laser microdissection followed by quantitative real-time PCR and PCR arrays, we performed a comprehensive expression profiling of 667 miRNAs in formalin-fixed, paraffin-embedded samples from the initial MI-FTC operation. Furthermore, we assessed the potential use of miRNAs as novel biomarkers for the metastatic potential of MI-FTC by logistic regression analysis. Comprehensive quantitative analysis of miRNA expression in MI-FTC samples revealed that the miR-221/222 cluster (i.e., miR-221, miR-222 and miR-222*), miR-10b and miR-92a were significantly upregulated in the M(+) group compared with the M(-) group. Interestingly, the expression levels of these miRNAs were also shown to be upregulated in widely invasive FTC (WI-FTC; n=13) that has distant metastasis and worse prognosis, indicating a close similarity in the miRNA expression between metastatic MI-FTC and WI-FTC. Logistic regression analysis revealed that miR-10b made a significant contribution to prognosis (OR 19.759, 95% CI 1.433-272.355, p=0.026). Our findings suggest that miR-10b is a potential prognostic factor for evaluating the metastatic potential of MI-FTC at an initial operation stage.
AuthorsTomoo Jikuzono, Masashi Kawamoto, Hiroshi Yoshitake, Kunio Kikuchi, Haruki Akasu, Hitoshi Ishikawa, Mitsuyoshi Hirokawa, Akira Miyauchi, Shinichi Tsuchiya, Kazuo Shimizu, Toshihiro Takizawa
JournalInternational journal of oncology (Int J Oncol) Vol. 42 Issue 6 Pg. 1858-68 (Jun 2013) ISSN: 1791-2423 [Electronic] Greece
PMID23563786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • MIRN10 microRNA, human
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MIRN92 microRNA, human
  • MicroRNAs
Topics
  • Adenocarcinoma, Follicular (genetics, pathology, surgery)
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor (genetics)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laser Capture Microdissection
  • Male
  • MicroRNAs (genetics)
  • Middle Aged
  • Paraffin Embedding
  • Predictive Value of Tests
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Thyroid Neoplasms (genetics, pathology, surgery)
  • Up-Regulation

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