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 micro-dissection 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.

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

“…Similar markers were proposed for minimally invasive FTCs. MiR-10b, -92a and -221/222 cluster were significantly elevated in a group of metastatic cancers, and the expression of miR-10b was proposed to be a prognostic factor for the evaluation of the metastatic potential of minimally invasive FTC with an ORZ19.8 (54). In a study by Xiong et al, the expression levels of miR-126-3p were negatively correlated with tumor size and worse clinical outcome of both FTC and PTC patients.…”

MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer

“…MiR-10b overexpression was first associated to metastasis in breast cancer [19], and subsequently confirmed as relevant to the development of metastasis in other types of cancer, such as nasopharyngeal [28], pancreatic [29], colorectal [30], hepatocellular [31][32][33][34], and follicular thyroid carcinoma [35]. MiR-9 up-regulation was associated with lymph node metastases in non-small cell lung cancer [36], hepatocellular carcinoma [37], breast [38,39] and colorectal cancer [40].…”

MicroRNA-92a promotes cell viability and invasion in cervical cancer via directly targeting Dickkopf-related protein 3

“…Among these cancer-related miR, miR-92a has been demonstrated to possess an oncogenic role in different cancer types, and several targets have been identified (13)(14)(15). A previous study indicated that miR-92a promoted the metastasis of colorectal cancer cells through inhibition of phosphatase and tensin homolog, leading to the upregulation of the phosphoinositide 3-kinase/protein kinase B pathway (13).…”