Our results show the potential importance of miR-221, miR-222, and miR-146b in determining the aggressive properties of PTCs and highlight the need to identify the gene targets of these miRNAs.

Context: Recent studies suggest that miR-146b deregulation in papillary thyroid carcinoma (PTC) was associated with advanced tumor characteristics. However, the influence of miR-146b expression on the prognosis of PTC remains unknown. We sought to correlate tumor expression levels of miR-146b with the prognosis of a previously reported PTC cohort and reveal the underlying mechanisms via a PTC cell line model. Methodology:Expression levels of miR-146b were assessed via quantitative real-time PCR in 71 cases of PTC with distinct clinico-pathogenetic characteristics. All patients were classified into the disease-free or active disease group, based on their medical records at the end of the follow-up period. In vitro gain-of-function experiments were performed in a BCPAP human papillary thyroid cancer cell line model, which harbored the homozygous mutation of BRAF. BCPAP cells were transfected with a mimic-miR-146b and nonspecific microRNA (miRNA) control to determine whether miR-146b overexpression promotes cell migration and invasion. Proliferation assay, colony formation assay, and chemotherapy-induced apoptosis were also determined. Results:Multivariate logistic regression analysis demonstrated advanced tumor stage, presence of cervical lymph node metastasis, and miR-146b expression were independent risk factors for poor prognosis in PTC. Patients with higher miR-146b expression levels had significantly poorer overall survival compared with those with lower miR-146b levels. The associated hazard ratio was 3.92 (95% confidence interval, 1.73-8.86, log-rank P Ͻ .05). Overexpression of miR-146b significantly increased cell migration and invasiveness. Furthermore, miR-146b also increased resistance to chemotherapy-induced apoptosis. Conclusions:Our results suggest that miR-146b is a novel prognostic factor of PTC. Furthermore, in vitro functional studies provided the mechanistic explanation for miR-146b in tumor aggressiveness. These results enhance understanding of the molecular mechanisms involved in tumor aggressiveness in PTC, provide new prognostic biomarkers, and ultimately offer new leads for developing therapies for PTC. (J Clin Endocrinol Metab 98: E196 -E205, 2013)

Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.

Our results demonstrated that IRAK1 is a direct target of miR-146b and has functional roles to inhibit various aggressive PTC cell activities. In conjunction with current therapeutic regimens, targeting the miR-146b-IRAK1 axis may provide a potential approach for PTC management.

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Purpose: To compare the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules (BTNs) among groups presenting with different nodule volumes. Materials and methods: This retrospective study evaluated 186 patients with BTNs who underwent ultrasound guided RFA treatment. The BTNs were categorized into small (10 ml); medium (10-30 ml); and large (>30 ml) according to the initial volume of BTNs before ablation. The RFA procedures were performed using the moving shot technique. The volume reduction ratio (VRR) of each nodule, cosmetic score, symptomatic score, and complications were analyzed at 1, 3, and 6 months after RFA treatment and the three groups compared. Results: At 1-month follow-up, the large nodules group showed significantly greater VRR compared to the other two groups (small, 31.88% ± 37.91; medium, 38.9% ± 19.18; large, 48.7% ± 20.43, p ¼ .03). At 6-month follow-up, there was no significant difference of VRR among the three groups (small, 74.6% ± 20.92; medium, 68.1% ± 17.07; large, 75.0% ± 11.88). The most common presented complication was temporary vocal palsy (6 patients; small, n ¼ 1; medium, n ¼ 1; large, n ¼ 3). Additionally, one skin burn, one hematoma, and one nodular rupture of BTNs occurred after the procedures. The complication rate of the large nodules group was highest among the three groups and showed a considerable difference (8 patients; small, n ¼ 1, 2.1%; medium, n ¼ 2, 4.5%; large, n ¼ 5, 11.4%, p ¼ .061). Conclusions: RFA was confirmed as effective in patients with large thyroid nodule (>30ml), with therapeutic efficacy similar to patients with smaller thyroid nodules.

ObjectiveThe application of radiofrequency ablation (RFA) for recurrent thyroid cancer has been demonstrated to effectively manage lesions at critical locations, such as abutting the trachea, with limited complications. Comprehensive investigation of both biochemical (B) and structural (S) change after RFA remains limited. We herein present the first single-center experience of RFA for the treatment of locoregional recurrent thyroid cancer in Taiwan.Design23 patients were enrolled, and the treatment responses after RFA were divided into four groups (E, S(+), B(+), and SB(+)), and then compared. The RFA technique, follow-up strategy, changes in pre-and post-operative status, and complications are presented. The volume reduction rate at 1, 3, and 6 months, and the differing responses between lesions abutting/not abutting the trachea are also discussed.ResultsIn patients with pre-RFA structural and biochemical incomplete (SB(+)) status, presenting with lesion with an initial maximum diameter of >3.2cm, a higher rate of structural incomplete status at the 6-month follow-up was noted in ROC analysis, with a sensitivity of 57% and specificity of 91%. Favorable structural remission after RFA was noted, and 60.9% of patients achieved biochemical complete status. No significant correlation was noted between the trachea-abutted lesion number and complete remission (p= 0.474). No significant difference in RFA efficacy was noted between the lesions abutting/not abutting the trachea.ConclusionsThis retrospective study reveals that RFA can achieve both structural and biochemical improvements for locoregionally recurrent thyroid cancer, with a low complication rate. Nearly half of the patients achieved an excellent response after RFA, while a favorable treatment response can be achieved despite the lesion abutting the trachea, with a mean VRR of 84.74%.

Background Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. Methods We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. Results During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.