title: 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.
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Jikuzono
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshitake
authors.forename: Kunio
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Haruki
authors.initials: H
authors.lastname: Akasu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimizu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takizawa
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C547183:MIRN10 microRNA, human; C525709:MIR221, human; C525710:MIR222, human; C541874:MIRN92 microRNA, human
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