ALKBH5-induced circular RNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2.

Although circular RNAs (circRNAs) are involved in cell proliferation, differentiation, apoptosis, and invasion, the underlying regulatory mechanisms of circRNAs in thyroid cancer have not been fully elucidated. This article aimed to study the role of circRNA regulated by N6-methyladenosine modification in papillary thyroid cancer (PTC). Quantitative real-time PCR, western blotting, and immunohistochemistry were used to investigate the expressions of circRNA nuclear receptor-interacting protein 1 (circNRIP1) in PTC tissues and adjacent noncancerous thyroid tissues. In vitro and in vivo assays were carried out to assess the effects of circNRIP1 on PTC glycolysis and growth. The N6-methyladenosine mechanisms of circNRIP1 were evaluated by methylated RNA immunoprecipitation sequencing, luciferase reporter gene, and RNA stability assays. Results showed that circNRIP1 levels were significantly upregulated in PTC tissues. Furthermore, elevated circNRIP1 levels in PTC patients were correlated with high tumor lymph node metastasis stage and larger tumor sizes. Functionally, circNRIP1 significantly promoted glycolysis, PTC cell proliferation in vitro, and tumorigenesis in vivo. Mechanistically, circNRIP1 acted as a sponge for microRNA (miR)-541-5p and miR-3064-5p and jointly upregulated pyruvate kinase M2 (PKM2) expression. Knockdown of m6 A demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) significantly enhanced circNRIP1 m6 A modification and upregulated its expression. These results show that ALKBH5 knockdown upregulates circNRIP1, thus promoting glycolysis in PTC cells. Therefore, circNRIP1 can be a prognostic biomarker and therapeutic target for PTC by acting as a sponge for oncogenic miR-541-5p and miR-3064-5p to upregulate PKM2 expression.

Clinical and ultrasonic risk factors for high-volume central lymph node metastasis in cN0 papillary thyroid microcarcinoma: A retrospective study and meta-analysis.

OBJECTIVE: Papillary thyroid microcarcinoma (PTMC) comprises more than 50% of all newly detected cases of papillary thyroid carcinoma (PTC). High-volume lymph node metastasis (involving >5 lymph nodes) (hv-LNM) is associated with PTMC recurrence. In half of the clinically node-negative (cN0) PTMC patients, central lymph node metastasis (CLNM) is pathologically present. However, clinical risk factors for high-volume CLNM (hv-CLNM) in cN0 PTMC have not been defined well. Therefore, we aimed to obtain evidence for hv-CLNM risk factors in cN0 PTMC. DESIGN: Data on patients who visited our hospital between January 2020 and December 2021 were collected; a preoperative diagnosis of cN0 and a postoperative pathological confirmation of PTMC were obtained. After filtering by inclusion versus exclusion criteria, the obtained data (N = 2268) were included in the meta-analysis. Relevant studies published as of 10 April 2022, were identified from the Web of Science, PubMed, WANFANG, and CNKI databases. These eligible studies were included in the meta-analysis and the association between clinicopathological factors and hv-CLNM in cN0 PTMC was assessed. SPSS and MetaXL were used for statistical analyses. RESULTS: The meta-analysis included 10 previous studies (11,734 patients) and 2268 patients enroled in our hospital for a total of 14,002 subjects. The results of which suggested that younger age (<40, odds ratio [OR] = 3.28, 95% confidence interval [CI] = 2.75-3.92, p < .001 or <45 odds ratio [OR] = 2.93, 95% CI = 2.31-3.72, p < .001), male sex (OR = 2.81, 95% CI = 2.25-3.52, p < .001), tumour size >5 mm (OR = 1.85, 95% CI = 1.39-2.47, p < .001), multifocality (OR = 1.88, 95% CI = 1.56-2.26, p < .001), extrathyroidal extension (OR = 2.58, 95% CI = 2.02-3.30, p < .001), capsule invasion (OR = 2.02, 95% CI = 1.46-2.78, p < .001), microcalcification (OR = 3.25, 95% CI = 2.42-4.36, p < .001) and rich blood flow (OR = 1.65, 95% CI = 1.21-2.25, p = .002) were the significant factors related to an elevated hv-CLNM risk in cN0 PTMC patients. Hashimoto thyroiditis (OR = 0.76, 95% CI = 0.55-1.07, p = .114), irregular margin (versus regular margin, OR = 0.96, 95% CI = 0.68-1.33, p = .787) and hypoechoic (versus nonhypoechoic, OR = 1.27, 95% CI = 0.84-1.92, p = .261) showed no significant association with hv-CLNM. CONCLUSIONS: Younger age, tumour size >5 mm, males, extrathyroidal extension, multifocality, microcalcification, capsular invasion, and rich blood flow were the significant clinicopathological risk factors for hv-CLNM risk in cN0 PTMC patients. These predictors may compensate for the sensitivity of imaging diagnosis in the preoperative period, thus helping in the effective identification of PTMCs with an invasive phenotype.

Incidental T1 stage medullary thyroid carcinoma: The effect of tumour diameter on prognosis and therapeutic implications.

OBJECTIVE: The definition of the tumour diameter of micro-medullary thyroid carcinoma (micro-MTC) is insufficient. It is controversial to perform a completion thyroidectomy immediately for incidental T1 stage MTC. DESIGN: We used the Surveillance, Epidemiology and End Results (SEER) registry to retrospectively analyze all patients with T1 stage MTC diagnosed between 2004 and 2015. The tumour diameter 1.0 and 0.5 cm were used as the cut-off points to group and analyze the differences of clinicopathological features. We analyzed the prognosis of patients with less than total thyroidectomy. METHODS: The disease-specific survival was the main outcome. Survival was estimated with Kaplan-Meier curves and Cox regression models estimated hazard ratios for tumour characteristics. RESULTS: A total of 908 patients diagnosed with T1 stage MTC in the SEER database were included. Our study found that tumour diameter 1.0 cm is a key point affecting the prognosis of T1 stage MTC patients, although patients with tumour diameter ≤ 0.5 cm had a lower rate of lymph node metastasis and no distant metastasis. Cox proportional hazard multivariate analysis showed that distant metastasis was the only risk factor for survival in patients with T1 stage MTC. Kaplan-Meier survival analysis showed that, regardless of tumour diameter, there was no significant difference between less than total thyroidectomy and total thyroidectomy in T1 stage patients. CONCLUSIONS: For incidental MTC with tumour diameter ≤ 1.0 cm and without distant metastasis, if there is no significant increase in serum calcitonin level after surgery and ret proto-oncogene (RET) gene mutation is negative, it may be not necessary to perform completion thyroidectomy immediately.

Microwave ablation of breast pseudoaneurysm.

Breast pseudoaneurysm is a very rare complication. In this study, we report a patient with huge breast pseudoaneurysm after ultrasound-guided vacuum-assisted biopsy (UGVAB) of breast nodules. In treatment, we used microwave ablation to treat the pseudoaneurysm, and then used UGVAB again to eliminate the complicated hematoma. The patients obtained good therapeutic effect. From this case, we experience that, before the interventional operations for breast nodules, the systematic ultrasound examination should be performed. In the needle entering channel, the obvious blood vessels should be avoided to reduce the unnecessary vascular injury. When the pseudoaneurysm occurs, the patient's condition, pseudoaneurysm situation and hematoma size should be comprehensively considered, combined with the multidisciplinary consultation, for selecting the best treatment strategy.

Clinicopathological Characteristics and Prognosis of Poorly Differentiated Thyroid Carcinoma Diagnosed According to the Turin Criteria.

OBJECTIVE: Poorly differentiated thyroid carcinoma (PDTC) is the primary cause of death in patients with nonanaplastic follicular cell-derived thyroid carcinoma. We purposed to identify the clinical and pathological characteristics of PDTC and their relationship with prognosis. METHODS: A retrospective analysis was conducted on patients diagnosed with PDTC at our institution from 2010 to 2018. All of their histopathology slides were reviewed by 2 experienced pathologists based on the Turin criteria. Furthermore, information regarding clinical characteristics, pathological characteristics, treatment strategy, and follow-up events were collected. The Kaplan-Meier method was used for survival analysis, while the log-rank test was used to compare survival curves. Then, the Cox proportional hazards model was used to perform univariate and multivariate analyses. RESULTS: Twenty-six patients with PDTC who met the Turin criteria were enrolled in this study. The median follow-up period of the included 26 patients was 76 months, while the 3- and 5-year survival rates were 40% and 18%, respectively. Notably, univariate analysis revealed that tumor size >4 cm (P = .038), extrathyroidal extension (ETE) (P = .020), distant metastases (P = .047), poorly differentiated areas >60% (P = .049), and Ki-67 labeling index >30% (P = .040) were associated with poor prognosis. On the other hand, multivariate analysis identified ETE (P = .007) and distant metastases (P = .031) as independent risk factors for poor prognosis. CONCLUSION: PDTC is a rare carcinoma with high invasiveness and poor prognosis. Patients with ETE or distant metastases may have adverse outcomes.

Calcitriol enhances Doxorubicin-induced apoptosis in papillary thyroid carcinoma cells via regulating VDR/PTPN2/p-STAT3 pathway.

There is increasing evidence that vitamin D deficiency is the risk factor for multiple diseases, such as immune disorder, cardiovascular disease and cancer. Calcitriol is the active form of vitamin D with beneficial effects on anti-cancer by binding vitamin D receptor (VDR). The primary aim of this study was to investigate the role of Calcitriol on papillary thyroid carcinoma (PTC) and explore the possible mechanism. We found nuclear VDR expression in PTC samples was negatively correlated with STAT3 hyperphosphorylation that indicated worse PTC clinicopathologic characteristics. Calcitriol treatment up-regulated VDR and protein tyrosine phosphatase N 2 (PTPN2) expression, down-regulated signal transducers and activators of transcription (STAT3) phosphorylation and thereby facilitating chemotherapy drug Doxorubicin-induced apoptosis in PTC cell lines. However, the apoptosis-promoting effect of Calcitriol and Doxorubicin co-treatment was abrogated by STAT3 hyperphosphorylation, indicating suppression of STAT3 phosphorylation was essential for combined treatment of Calcitriol and Doxorubicin in PTC. Together, these results suggested that Calcitriol reinforced the sensitivity of PTC cells to Doxorubicin by regulating VDR/PTPN2/p-STAT3 signalling pathway.

Long noncoding RNA SAMMSON promotes papillary thyroid carcinoma progression through p300/Sp1 axis and serves as a novel diagnostic and prognostic biomarker.

Accumulating evidence suggests that long noncoding RNA (lncRNA) plays a fundamental role in cancer progression. However, its biological function in papillary thyroid carcinoma (PTC) has not been fully elucidated. Here, we deciphered the essential role of lncRNA SAMMSON in PTC. SAMMSON was identified to be notably upregulated in PTC cells, tissues, and plasma, and could be used as an effective diagnostic and prognostic biomarker for PTC patients. Knockdown of SAMMSON significantly inhibited PTC cell proliferation and invasion in vitro as well as tumorigenicity and metastasis in vivo. Mechanistically, SAMMSON was transcriptionally elevated by oncogenic Sp1, in turn, upregulated SAMMSON was capable of acting as a scaffold to recruit p300 to increase H3K9ac and H3K27ac levels on Sp1 promoter region, leading to transcriptional activation of Sp1, thereby facilitating PTC progression. Taken together, our data demonstrate that SAMMSON is an oncogenic lncRNA and unveil the crucial role of SAMMSON/Sp1 positive feedback loop in tumorigenesis and aggressiveness of PTC.

Unilateral Tnm T1 And T2 Papillary Thyroid Carcinoma With Lateral Cervical Lymph Node Metastasis: Total Thyroidectomy or Lobectomy?

OBJECTIVE: The aim of this study was to explore the effect of total thyroidectomy (TT) and lobectomy (LT) on the prognosis of unilateral papillary thyroid carcinoma (PTC) with lateral cervical lymph node metastasis. METHODS: Patients with PTC and lateral cervical lymph node metastasis who underwent lateral cervical lymph node dissection between January 2007 and December 2016 were retrospectively reviewed. To investigate the effect of surgical procedure on the prognosis of lymph node metastasis patients, other high-risk factors such as extrathyroidal invasion and large tumor size were excluded. All patients were in Tumor-Node-Metastasis (TNM) stage T1 and T2. Primary end point was recurrence-free survival (RFS). RESULTS: Among 264 PTC patients, 104 (39.4%) patients received TT and 160 (60.6%) patients received LT. With a median follow-up of 50 months (interquartile range, 34 to 74 months), 7 patients (2.65%) experienced recurrence. The 5-year RFS in the TT and LT groups was 96.1% and 97.7%, respectively, and was not significantly different (P = .765). Similar results were found when excluding patients who received radioiodine ablation, which were 97.7% and 97.4%, respectively (P = .752). Age ≥55 years (hazard ratio, 7.368; P = .018) and multifocality in the ispi-lateral lobe (hazard ratio, 10.059; P =.006) were identified as independent risk factors of recurrence. CONCLUSION: For unilateral TNM T1 and T2 PTC patients with lateral lymph node metastasis, there was no significant difference in the effect of TT and LT for RFS in the absence of other risk factors during the follow-up period. Patient age ≥55 years with multifocality in the unilateral lobe might be independent risk factors for prognosis.

Surgery After Ultrasound-Guided Radiofrequency Ablation for Papillary Thyroid Carcinoma in 21 Patients: A Retrospective Study from a Single Center in China.

BACKGROUND Radiofrequency ablation (RFA) is used to treat various cancers, but its use in thyroid cancer remains controversial. The aim of this study was to investigate surgical findings after RFA for papillary thyroid cancer (PTC). MATERIAL AND METHODS The study included 21 patients (average age 44.9±13.3 years) who had biopsy-confirmed thyroid cancer treated with RFA in multiple hospitals. Surgery was done in the First Hospital of China Medical University. RESULTS The 21 patients had a total of 32 thyroid nodules that were treated with RFA. Twenty-eight nodules were malignant, and 4 nodules were benign. Before RFA, 17 of the malignant nodules were >1 cm and 11 were ≤1 cm. Among the 28 malignant nodules, post-ablation lesions adhered to or invaded the structures surrounding the thyroid in 17 (60.7%), 19 (67.9%), and 22 (78.6%) nodules evaluated with ultrasound, contrast-enhanced computed tomography, and intraoperatively, respectively. Based on pathology results, 7 (33.3%) of the 21 patients had bilateral cancer. Ten (47.6%) of the 21 patients had central lymph node metastasis and 2 (9.5%) had lateral lymph node metastasis. For 5 (15.6%) of the 32 nodules, the fine-needle aspiration results were not consistent with the postoperative pathological results. Five (23.8%) of the 21 patients with lymph node metastasis had clinically negative (CN0) lesions. CONCLUSIONS RFA for PTC primary lesions may be incomplete and leave residual lymph node metastasis, even in lesions ≤1 cm. RFA should be recommended with caution in the treatment of operable patients with primary PTC.

Comparison of Outcomes Following Thyroid Isthmusectomy, Unilateral Thyroid Lobectomy, and Total Thyroidectomy in Patients with Papillary Thyroid Microcarcinoma of the Thyroid Isthmus: A Retrospective Study at a Single Center.

BACKGROUND Papillary thyroid microcarcinoma (PTMC) measures less than 10 mm in diameter, is more common in the thyroid lobes, but rarely presents in the thyroid isthmus. This retrospective study aimed to compare patient outcomes following various types of surgery in patients with PTMC of the thyroid isthmus, at a single center in China. MATERIAL AND METHODS We analyzed the clinical data of patients with isthmus thyroid cancer treated at the First Hospital of China Medical University. Patients were divided into 2 groups according to the tumor diameter-PTMC of the thyroid isthmus and papillary thyroid carcinoma >10 mm. The clinicopathological features between the 2 groups were compared, and the effects of various surgical methods on the prognosis of patients were analyzed. RESULTS A total of 70 patients were included in this study: 29 with PTMC of the thyroid isthmus (41.4%) and 41 with papillary thyroid carcinoma >10 mm (58.6%). The rates of lymph node metastasis (10.3% vs. 34.1%) and extrathyroid extension (0% vs. 14.6%) in the PTMC of the thyroid isthmus were significantly lower than those in the papillary thyroid carcinoma >10 mm. The recurrence-free survival (RFS) rate was 97.1%. Survival analysis showed that there was no significant difference in RFS among patients with PTMC of the thyroid isthmus undergoing isthmusectomy, unilateral lobectomy, and total thyroidectomy. CONCLUSIONS These findings from a single center showed that for patients with PTMC of the thyroid isthmus, who had no comorbidities, there was no significant difference in outcome between the 3 types of thyroid surgery.

IL-34 is a potential biomarker for the treatment of papillary thyroid cancer.

BACKGROUND: Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine and is a vital regulator in different tumor types. However, the function of IL-34 in thyroid carcinoma has yet to be investigated. In this study, we analyzed the expression of IL-34 in human papillary thyroid cancer (PTC) samples and determined its effects on the proliferation and apoptosis of PTC cells. METHODS: We examined the expression of IL-34 in serum and tissue samples of patients with PTC by Western blotting and ELISA assay and analyzed its association with clinicopathological features including tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis (LNM). We selected TPC1 and K1 for knockdown or overexpressing of IL-34 via small interference RNA transfection. The proliferation of PTC cells was evaluated by CCK8 assay. We further investigated the role of IL-34 in apoptosis by flow cytometry and studied the protein levels of epithelial-mesenchymal transition (EMT) biomarkers, phosphorylated extracellular-regulated kinase (ERK), and total-ERK (t-ERK) by Western blotting. RESULTS: Our results show that IL-34 is significantly upregulated in serum and tissue samples from patients with PTC. IL-34 promotes the proliferation and suppresses apoptosis in PTC cells. In addition, IL-34 can promote the EMT and activate ERK signaling pathway in PTC cells. CONCLUSION: This study provides novel evidence that IL-34 serves as an oncogene in PTC. IL-34 promotes proliferation, EMT phenotype, and ERK signaling pathway and inhibits apoptosis in PTC cells. Therefore, IL-34 may be a potent therapeutic target for the treatment of PTC.

Use of Delphian lymph node metastasis to predict central and lateral involvement in papillary thyroid carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Whether Delphian lymph node (DLN) metastasis is a reliable predictor of widespread lymph node metastasis in papillary thyroid carcinoma (PTC) remains controversial. This meta-analysis investigated the value of DLN metastasis for predicting central and lateral involvement in PTC. DESIGN AND METHODS: A literature search using the PubMed, SCIE and the Chinese National Knowledge Infrastructure (CNKI) databases was conducted. Two reviewers independently extracted data and evaluated the studies for inclusion. Fixed-effects and random-effects models were used to analyse the data based on their heterogeneity. A sensitivity analysis was performed, and publication bias was assessed using Begg's funnel plot and Egger's linear regression test. RESULTS: Data from 10 studies were analysed. The risk of central lymph node (CLN) metastasis was significantly higher in the DLN-positive group than in the DLN-negative group (OR = 9.05, 95% CI: 5.13-15.99) with moderate heterogeneity (P = 0.022, I2  = 53.5%). The risk of lateral lymph node (LLN) metastasis was significantly higher in the DLN-positive group than in the negative group (OR = 10.88, 95% CI: 7.60-15.58), with low heterogeneity (P = 0.603, I2  = 0.0%). Sensitivity analysis indicated that the results were stable and credible, and no publication bias was found. CONCLUSIONS: Delphian lymph node metastasis is valuable for predicting central and lateral compartment involvement in patients with PTC. The DLN of PTC patients should be dissected intraoperatively and sent for frozen section consultation. If the result is positive, the CLNs should be thoroughly dissected and the LLNs should be further evaluated.

Reduced expression of oestrogen receptor-ß is associated with tumour invasion and metastasis in oestrogen receptor-α-negative human papillary thyroid carcinoma.

Oestrogens play an important role in the development and progression of papillary thyroid carcinoma (PTC) through oestrogen receptor (ER)-α and -ß, which may exert different or even opposing actions in PTC. The roles of ERß in ERα-negative PTC are still not clear. This study investigated the expression dynamics of ERß1 (wild-type ERß) and its clinical significance in female ERα-negative PTC patients. ERß1 expression was detected in thyroid tissues of 136 female patients diagnosed with PTC. The relationships between ERß1 expression and clinicopathological/biological factors were also analysed in female ERα-negative PTC patients. The total score for ERß1 was significantly lower in female ERα-negative PTC patients with LNM or ETE when compared to those without LNM or ETE (Z = -2.923, P = 0.003 and Z = -3.441, P = 0.001). Accordingly, the total score for ERß1 was significantly higher in ERα-negative PTC patients expressing E-cadherin compared to patients negative for E-cadherin expression (Z = -2.636, P = 0.008). The total score was lower in ERα-negative PTC patients positive for VEGF expression compared to those negative for VEGF expression (Z = -1.914, P = 0.056). This preliminary study indicates that reduced expression of ERß1 in female ERα-negative PTC patients is associated with greater progression of the disease. This may provide insights into the underlying molecular mechanisms of ERß1 and could help design targeted approaches for treating or even preventing this disease.

Outcome of Thyroid Carcinoma Showing Thymus-Like Differentiation in Patients Undergoing Radical Resection.

BACKGROUND: Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor of the thyroid. It is difficult to diagnose, and there is no universally recognized therapeutic regimen. This study aims to define the clinicopathological features and discuss the optimal management of CASTLE. METHODS: We retrospectively analyzed six patients with CASTLE who accepted surgery at the First Hospital of China Medical University between January 2010 and December 2015. RESULTS: The six patients (three women and three men) had median age of 53 years (range 47-61 years). All patients presented with a slow-growing, painless neck mass; three patients also had hoarseness. All tumors were located in middle-lower or lower lobe, and two tumors extended to the substernal region. All patients underwent radical surgery without postoperative radiotherapy or chemotherapy. Five patients had extrathyroidal extension and two had lymph node metastasis. All six tumors were positive for CD5 and negative for thyroglobulin (Tg) and thyroid transcription factor (TTF)-1. Median follow-up was 32 months (range 23-81 months). Lateral cervical lymph node metastasis occurred in one patient at 26 months after initial treatment. CONCLUSIONS: CASTLE is a rare, aggressive malignant tumor of the thyroid. Ultrasound, computed tomography, and fine-needle aspiration biopsy may not be sufficient to establish the diagnosis preoperatively; pathological examination and immunohistochemistry, particularly positive CD5 staining, are necessary to establish the diagnosis. Patients with CASTLE can yield a favorable outcome after radical surgery.

Potential Use of 1-25-dihydroxyvitamin D in the Diagnosis and Treatment of Papillary Thyroid Cancer.

BACKGROUND Low levels of 1-25-dihydroxyvitamin D3 [1,25(OH)2D3] in serum may be a risk factor for several tumor types. Also, high cathelicidin antimicrobial peptide (CAMP) expression is regarded to be important against tumor progression. We evaluated the potential importance of 1,25(OH)2D3 in the diagnosis and treatment of papillary thyroid cancer (PTC). MATERIAL AND METHODS The preoperative serum level of 1,25(OH)2D3 was measured using a double-antibody sandwich enzyme-linked immunosorbent assay. Vitamin D3 receptor (VDR) expression was detected by streptavidin-peroxidase immunohistochemical staining in PTC specimens. Receiver operating characteristic (ROC) curves were created to assess the diagnostic value of 1,25(OH)2D3. The effect of 1,25(OH)2D3 on the proliferation and apoptosis of PTC cell lines were studied by Cell Counting Kit (CCK)-8 assay and Annexin V/propidium iodide staining, respectively. CAMP expression was measured by qRT-PCR and western blotting. Short interfering RNAs were used to reduce CAMP expression in PTC cell lines. RESULTS The preoperative serum level of 1,25(OH)2D3 in PTC was obviously lower than that in nodular goiter (NG) (P<0.05). The ROC curve suggested that 1,25(OH)2D3 might serve as a potential diagnostic value at a cutoff of 20.13 pg/mL, The VDR showed higher expression in PTC than in paired adjacent non-cancerous tissue. 1,25(OH)2D3 inhibited the proliferation and induced the apoptosis of PTC cells, and increased CAMP expression significantly, whereas CAMP knockdown demonstrated opposite effects. CONCLUSIONS 1,25(OH)2D3 may be a new, potential biomarker for the identification of PTC and NG. It may also become 1,25(OH)2D3 may a potential target for drug action to treat PTC through CAMP.

HSP90 inhibitor NVP-AUY922 induces cell apoptosis by disruption of the survivin in papillary thyroid carcinoma cells.

Heat shock protein 90 (HSP90) is a molecular chaperone required for maintaining the stability and function of signal proteins that plays an important role in promoting the growth and survival of cancer cells. The incidence of papillary thyroid carcinoma (PTC) has been increasing in recent years. The effect of the novel non-geldanamycin HSP90 inhibitor NVP-AUY922 on apoptosis of papillary thyroid carcinoma cells has not been investigated. The influence of AUY922 on the survival of PTC cell lines K1 and IHH4 was evaluated. Cell viability was determined by cell counting kit method. Cell apoptosis was assessed by flow cytometry and western blotting and the potential mechanism was evaluated by western blotting and immunoprecipitation. Overexpression plasmid was transfected by Lipofectamine 2000 method. In K1 and IHH4 cell lines, after the treatment of AUY922, cell viability decreased, and the proportion of apoptosis cells increased. AUY922 caused the cleavage of PARP and caspase-3 proteins, and altered expression of survivin, which was a client protein of HSP90. In AUY922-treated cells, overexpression of survivin attenuated growth inhibition and cell apoptosis. The results indicate that AUY922 induces apoptotic cell death in PTC cells. Moreover, our findings demonstrate that AUY922 induced apoptosis by downregulating the expression of survivin protein in PTC cells.

A meta-analysis of intraoperative neuromonitoring of recurrent laryngeal nerve palsy during thyroid reoperations.

BACKGROUND: The rate of recurrent laryngeal nerve (RLN) palsy, a common complication of thyroid surgery, is especially high in thyroid reoperations. The present meta-analysis assesses whether intraoperative neuromonitoring (IONM) reduces the prevalence of RLN palsy in thyroid reoperations. DESIGN AND METHODS: A systematic literature search was conducted in the PubMed, SCIE and Wan Fang databases for studies published up to 31 August 2016. All data were analysed using STATA (version 11) software. Publication bias was assessed using Begg's funnel plot and Egger's test, and sensitivity analysis was performed. RESULTS: Nine studies including 2436 at-risk nerves met the inclusion criteria. The results were presented as pooled relative risks (RRs) with 95% confidence intervals (CI). The overall RLN palsy rate was significantly lower in reoperations conducted with IONM than in those conducted without IONM (RR=0.434, 95% CI=0.206-0.916, P=.029). High heterogeneity was found (I2 =70.2%, P=.001). The rates of transient RLN palsy with and without IONM did not differ significantly (RR=0.607, 95% CI=0.270-1.366, P=.227). The heterogeneity was high (I2 =67.4%, P=.005). However, IONM was significantly associated with a reduction in permanent RLN palsy (RR=0.426, 95% CI=0.196-0.925, P=.031). No significant heterogeneity was found (I2 =13.7%, P=.325). Funnel plots for overall and transient RLN palsy showed a possible publication bias. CONCLUSIONS: Intraoperative neuromonitoring (IONM) is associated with a reduction in overall and permanent RLN palsy in thyroid reoperations. However, given the limited sample size and heterogeneity in this meta-analysis, further studies are required to confirm our preliminary findings.

MicroRNA-663 suppresses cell invasion and migration by targeting transforming growth factor beta 1 in papillary thyroid carcinoma.

MicroRNA-663 (miR-663) has been detected in a large variety of tumor types; however, it still holds both tumor suppressive and oncogenic roles in different tumor types. The miRNA-CHIP microarray assay revealed downregulation of miR-663 in papillary thyroid carcinoma (PTC); however, the effect of miR-663 on PTC cell invasion and migration remains unknown. Accordingly, this study aimed to investigate the potential involvement of miR-663 in PTC. In this study, miR-663 expression level was measured via quantitative real-time PCR in 91 pairs of human PTC and adjacent normal tissues and in two human PTC cell lines. The effect of miR-663 on PTC cell invasion and migration were studied by transwell and wound healing assays. In addition, the miR-663 target was searched and the underlying mechanism was clarified by reporter assay and rescue experiment. The current study confirmed that miR-663 expression was inhibited in PTC tissue samples and PTC cell lines. There were statistically significant differences in expression of miR-663 with regard to age and tumor size. Upregulation of miR-663 suppressed PTC cell invasion and migration. Further study showed that transforming growth factor beta 1 (TGFß1) was the direct target of miR-663 and mediated the effect of miR-663 on PTC development. By targeting TGFß1, miR-663 efficiently regulates the expression of epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs). The data indicated that miR-663 may suppress tumor invasion and migration by targeting TGFß1 and regulate EMT progress of PTC cells.

Downregulation of long noncoding RNA NONHSAT037832 in papillary thyroid carcinoma and its clinical significance.

Long noncoding RNA (lncRNA) is a kind of RNA that is longer than 200 nucleotides with limited or no protein-coding potential. Studies have proved that lncRNAs play important regulatory roles in gene expression and contribute to oncogenesis and cancer metastasis. However, the expression level of lncRNAs and their clinicopathologic significance in papillary thyroid carcinoma (PTC) have not been well studied. In this study, we investigated the expression level of a novel lncRNA NONHSAT037832 in PTC and paired noncancerous thyroid tissues as well as some cell lines by quantitative real-time polymerase chain reaction. The association between the expression level of NONHSAT037832 and clinicopathologic characteristics of patients with PTC was further analyzed. Three receiver operating characteristic curves (ROCs) were established to evaluate the diagnostic value of NONHSAT037832. The results suggested that the expression level of NONHSAT037832 was significantly decreased in PTC compared with paired noncancerous tissues (P < 0.01). And, NONHSAT037832 was also significantly downregulated in two PTC cell lines (K1 and IHH-4) compared to normal thyroid follicular epithelial cell line Nthy-ori 3-1 (P < 0.01). Downregulated NONHSAT037832 was significantly associated with lymph node metastasis (P = 0.015) and tumor size (P = 0.032). The ROCs revealed that NONHSAT037832 had a high diagnostic value for differentiating between PTC and noncancerous diseases as well as identifying PTC with lymph node metastasis and larger tumors (≥3 cm). The area under curve was up to 0.897 (95%CI = 0.852-0.942, P = 0.000), 0.641 (95%CI = 0.519-0.762, P = 0.033), and 0.702 (95%CI = 0.567-0.827, P = 0.008), respectively. This study indicated that NONHSAT037832 might serve as a potential biomarker of PTC.

Differential expression patterns and clinical significance of estrogen receptor-α and ß in papillary thyroid carcinoma.

BACKGROUND: The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and ß1 (wild-type ERß), in PTC tissue and their clinical significance. METHODS: Immunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n =89) and nodular thyroid goiter (NTG; n =30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed. RESULTS: The positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18-45 years old; n =50) than age-matched female NTG patients (n =30), while ERß1 exhibited the opposite pattern. There was no difference in ERα or ERß1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n =39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERß1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERß1 expression when compared with those with extranuclear ERß1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERß1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases. CONCLUSIONS: The differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful immunohistochemical marker for differential diagnosis of PTC. The associations of ER subtype expression with Ki-67, mutant P53, VEGF expression and ETE in female PTC patients of reproductive age suggest that estrogen-activated ERα may mediate stimulatory effects on PTC growth and progression whereas ERß1 has some inhibitory actions.