Search

Background: Few studies have been conducted on the dynamic survival rates of follicular thyroid cancer (FTC). This study aimed to ascertain how the survival probability of patients with FTC changes over time. Methods: In this retrospective analysis, 10,617 patients diagnosed with FTC between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were included. Actuarial disease-specific survival (DSS) was estimated using the Kaplan-Meier method, and the log-rank test was used for comparisons. The annual hazard of mortality was determined using the hazard function, and the conditional survival (CS) was calculated using the life table method. Results: A total of 459 (4.3%) patients died of FTC, and the 5-year and 10-year DSS rates were 96.6 ± 0.2% and 94.6 ± 0.3%, respectively. There was a statistically significant difference in the DSS rate between patients with different SEER combined summary stages (P < 0.001). The annual hazard curve for cancer mortality in the entire study cohort displayed a steep downward trend with a slight peak at 2.5 years after diagnosis, followed by a gradual decline. Patients with distant metastases exhibited a higher mortality hazard curve and more notable declining trend. CS demonstrated an upward trend across the entire study population, with the most pronounced trend in patients with distant metastases. Conclusion: Prognosis improved over time in a stage-dependent manner in patients with FTC after diagnosis. The most significant improvement was observed in the patients with distant metastases. Notably, dynamic survival estimations, such as death hazard and conditional survival analysis, provide more precise survival projections than traditional survival analysis for FTC survivors. [ABSTRACT FROM AUTHOR]

Background: Limited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC). Methods: In this retrospective study, nationwide data from the Surveillance, Epidemiology, and End Results database (1992-2020) were utilized. The Accelerated Failure Time Model was applied to calculate Survival Time Ratios (TR), with the primary focus on mortality resulting from DTC. The competing risks model was employed to investigate the relative risks of various outcomes in DTC patients with a survival duration of 5 years or more. Results: In our cohort, 279 patients succumbed to DTC, while 748 died from other diseases. Notably, in DTC cohorts, noncancer-specific mortality rates were consistently higher than DTC-specific mortality rates across different age groups and genders. The risk of DTC and noncancer-specific mortality varied based on the TNM stage. With more advanced disease stages, the risk of DTC and other cancer-specific mortality gradually increased. The cumulative mortality from other cancer-specific causes was consistently the lowest. Conclusions: In long-term surviving DTC patients, noncancer-specific mortality outweighed DTC-specific mortality irrespective of age and gender. For stage I and II patients, increased attention should be directed toward noncancer-specific mortality in postoperative follow-ups. Conversely, for stage III and IV patients, greater consideration should be given to DTC-related causes of death. In addition, for stage III and IV DTC patients, the risk of death from other cancers was significantly higher than for stages I and II. [ABSTRACT FROM AUTHOR]

By testing and analyzing the electrical characteristic data of signal equipment, it is possible to grasp the trend of equipment operation status and detect abnormal performance of signal equipment in advance. The electrical characteristic parameter indicators of signal equipment are related to their working modes. When the signal equipment operates in diff erent working modes, the magnitude of its operating voltage, current, and other values will change with changes in the working mode. In the case of multi-mode mixed-sampling statistics, it is difficult to quickly distinguish between normal and abnormal changes in data. Taking signal equipment such as tracks and switches as examples, this study explores new ideas for statistical analysis of operating trends of signal equipment in multi-state mode through working mode recognition, data sampling, and statistical analysis of electrical characteristics trends in diff erent modes. [ABSTRACT FROM AUTHOR]

Background: There are conflicting reports on the factors that increase the likelihood of patients dying from follicular thyroid carcinoma (FTC). Therefore, it is critical to identify risk factors of patients with FTC. This study aimed to identify the factors that increase the risk of death of patients with FTC and help clinicians make better treatment and follow-up decisions. Methods: A systematic literature review was conducted in PubMed and Web of Science databases for relevant studies published before January 31, 2023. Their reference lists were also analyzed. Two reviewers extracted data and evaluated the quality of eligible studies independently. Studies on patients who had open thyroidectomy procedures with or without neck dissection were included in this review. The RevMan 5.3 software was used to analyze the data. Results: This meta-analysis included thirteen studies with a total of 2075 patients. The following variables were associated with an increased risk of death in FTC patients: age > 45 years, male, tumor diameter > 4 cm, multifocality, extrathyroidal extension (ETE), widely invasive (WI), cervical lymph node metastasis (CLNM), distant metastases (DM) and non-radical resection tumor. Lobectomy and no radioactive iodine (RAI) treatment was not associated with the death of FTC patients. Conclusion: Clinicians should pay closer attention to the following significant risk factors associated with the death of FTC patients: age (> 45), male, multifocality, tumor diameter > 4 cm, ETE, WI, non-radical resection tumor, CLNM, and DM. Individualized initial treatment and close follow-up are needed FTC patients who have these risk factors. [ABSTRACT FROM AUTHOR]

Background: Little is known about death hazard and conditional survival of oncocytic cell carcinoma of the thyroid (OCC). Methods: Patients diagnosed with OCC between 2004 to 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier method was used to estimate the actuarial disease-specific survival (DSS). The annual hazard rate of death was depicted employing the hazard function. Based on the life-table method, the conditional DSS was calculated. Results: In terms of DSS rates, there were statistically significant differences among the different stages (P < 0.01). Annual hazard curves for mortality from OCC in the entire study participants demonstrated an overall decreasing tendency with two peaks at 3 and 10 years. In patients with distant disease, the death risk curve was the steepest and decreased quickly and evidently. Conditional DSS tended to increase over time in the entire study population. Patients with distant disease showed more significant alterations than those patients with local or regional disease. Conclusions: Prognosis improved over time in patients with OCC. The largest increase in conditional DSS was observed in patients with distant disease. Conditional survival may provide more relevant prognostic information than conventional survival estimates and allow personalized follow-up and counseling. Key points: Questions: How do the risk of death and survival probability change over time in patients with oncocytic cell carcinoma of the thyroid (OCC)? Findings: In this retrospective study of 3401 patients, prognosis improves over time in patients with OCC of different Surveillance, Epidemiology, and End Results (SEER) stages. The greatest improvement was observed in patients with distant disease. Meaning: For OCC survivors, death hazard and conditional survival analysis provide more accurate dynamic estimates of survival than conventional survival analysis for patients who have survived a period of time after diagnosis. With such information, clinicians can provide an accurate risk assessment of survival and formulate individual treatment and surveillance recommendations for patients diagnosed with OCC. [ABSTRACT FROM AUTHOR]

Background: Lateral lymph node metastasis (LLNM) is common in patients with papillary thyroid cancer (PTC), usually occurring after central lymph node metastasis (CLNM). However, some patients experience LLNM without first developing CLNM. This study aimed to identify the risk factors for developing LLNM without CLNM. Methods: We retrospectively reviewed 421 patients diagnosed with PTC who underwent lobectomy or total thyroidectomy with central and ipsilateral lateral lymph node dissection. We collected clinicopathological data and used univariate and multivariate logistic regression analyses to determine the risk factors associated with LLNM without CLNM. Results: The LLNM without CLNM frequency was 18.3% (77/421). Univariate analyses demonstrated that age over 55 years, primary tumor in the upper portion of the thyroid, the number of central lymph node (CLN) and LLNM, primary tumor size, and the summed size of multi‐foci tumors smaller than 1 cm were significantly associated with LLNM without CLNM (p < 0.05). Multivariate analysis revealed that LLNM without CLNM was more likely to occur in patients aged ≥55 years (odds ratio [OR], 2.309; 95% confidence interval [CI], 1.133–4.704; p = 0.021), and primary tumor in the upper portion of the thyroid (OR, 0.524; 95% CI, 0.295–0.934; p = 0.028). Conclusion: The lymph node metastasis pattern in patients with PTC is not constant. Therefore, surgeons should evaluate the lateral lymph nodes, especially in patients older than 55 years or when the primary tumor is in the upper portion of the thyroid. [ABSTRACT FROM AUTHOR]

B Dear Editor: b The incidence of papillary thyroid cancer (PTC) has increased substantially worldwide in the recent decades.[1] Generally, PTC has an indolent course and a favorable prognosis, with a 10-year disease-specific survival (DSS) of more than 95%.[2] However, patients with distant metastases have a substantially lower 10-year DSS rate (~50%).[3] Moreover, since the 1980s, the incidence of differentiated thyroid cancer with distant metastasis has been steadily increasing in the United States.[3] Traditionally, survival rates are estimated from the time of diagnosis. The 5-year conditional DSS improved gradually in patients with lung metastasis, whereas it worsened in patients with bone metastasis farther from the diagnosis (Fig. The death hazard rate of patients with distant metastasis was higher than that of patients with localized or regional disease during the entire follow-up period (Fig. Among patients with single-site metastasis, patients with lung metastasis had the highest death hazard rate (0.07 [CI: 0.06-0.08]) during the first 2.5 years; thereafter, those with bone metastasis had the highest death hazard rate (0.08 [CI: 0.07-0.09]) (Fig. [Extracted from the article]

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine-related malignancy. In spite of the good prognosis, a more aggressive disease can develop in some PTC patients, leading to poor survival. Nuclear paraspeckle assembly transcript 1 (NEAT1) enhances tumorigenesis; however, the relationship between NEAT1_2 and glycolysis in PTC has not been identified. The expressions of NEAT1_2, KDM5B, Ras-related associated with diabetes (RRAD), and EHF were determined by quantitative reverse transcription polymerase chain reaction and immunocytochemistry. The effects of NEAT1_2, KDM5B, RRAD, and EHF on PTC glycolysis were ascertained employing in vitro as well as in vivo experiments. Chromatin immunoprecipitation (ChIP), RNA binding protein immunoprecipitation, luciferase reporter assays, and co-immunoprecipitation were utilized to analyze the binding abilities among NEAT1_2, KDM5B, RRAD, and EHF. Overexpression of NEAT1_2 was associated with glycolysis in PTC. NEAT1_2 could activate glycolysis by regulating the expression of RRAD in PTC. NEAT1_2 mediated H3K4me3 modification at the promoter of RRAD by recruiting KDM5B. RRAD further negatively regulated glycolysis by binding and regulating the subcellular location of the transcription factor EHF. EHF could activate the transcription of NEAT1_2, hexokinase 2, and pyruvate kinase M2, thereby forming the NEAT1_2/RRAD/EHF feedback loop. Our study revealed that the NEAT1_2/RRAD/EHF positive feedback loop facilitated glycolysis in PTC, which might avail meaningful insight for PTC management. [ABSTRACT FROM AUTHOR]

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 m6A demethylase α‐ketoglutarate‐dependent dioxygenase alkB homolog 5 (ALKBH5) significantly enhanced circNRIP1 m6A 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. [ABSTRACT FROM AUTHOR]

Our study is the first to estimate the survival of patients with ATC using annual hazard rate of cancer mortality and conditional survival (CS). B Dear Editor: b Anaplastic thyroid cancer (ATC) is a rare but highly aggressive and lethal type of thyroid cancer with a steadily increasing incidence for the past few decades.[1] Multidisciplinary interventions combining surgery, radiation therapy, and/or chemotherapy are usually the mainstay treatment options for ATC to control this ominous disease.[2] However, the prognosis remains poor. When stratified based on TNM stage, the death hazard curve of patients with stage IVC disease was the highest and declined more rapidly and obviously than that of patients with stage IVB and IVA disease until two years after diagnosis. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the predictive value of the extent of metastatic lymph nodes in the central and lateral neck compartment for recurrence in papillary thyroid cancer (PTC) patients with pathologically lateral lymph node metastasis (pN1b). Methods: This study enrolled 252 patients with pN1b from PTC. Results: During a mean follow‐up of 17.6 years, 55 (21.8%) patients experienced recurrence. Patients with palpable lymph nodes were more likely to have a recurrence than those with nonpalpable lymph nodes (30.1% vs. 17.8%, relative risk 1.7, 95%CI: 1.1–2.7). For patients with palpable metastatic lymph nodes, lymph node ratio of lateral lymph nodes ≥0.5 (aHR = 2.906, 95%CI: 1.29–6.54) and age ≥55 years (aHR = 2.508, 95%CI: 1.12–5.63) were independent prognostic factors. For those without palpable nodes, age ≥55 years (aHR = 2.224, 95%CI: 1.08–4.60) and tumor size >4 cm (aHR = 2.168, 95%CI: 1.01–4.66) were independently predictive of worse RFS. Conclusions: Palpable lymph nodes were approximately twice as likely to recur as nonpalpable nodes. Metastatic lateral lymph node ratio predicts recurrence in pN1b PTC patients with palpable lymph nodes, but not those without ones. [ABSTRACT FROM AUTHOR]

Background: N6-methyladenosine (m6A) modification is the most common chemical modification in mammalian mRNAs, and it plays important roles by regulating several cellular processes. Previous studies report that m6A is implicated in modulating tumorigenesis and progression. However, dysregulation of m6A modification and effect of m6A demethylase fat-mass and obesity-associated protein (FTO) on glucose metabolism has not been fully elucidated in papillary thyroid cancer (PTC). Methods: Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry were performed to explore the expression profile of FTO in PTC tissues and adjacent non-cancerous thyroid tissues. Effects of FTO on PTC glycolysis and growth were investigated through in vitro and in vivo experiments. Mechanism of FTO-mediated m6A modification was explored through transcriptome-sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP-qPCR, luciferase reporter assays, RNA stability assay and RNA immunoprecipitation assay. Results: FTO expression was significantly downregulated in PTC tissues. Functional analysis showed that FTO inhibited PTC glycolysis and growth. Further analyses were conducted to explore FTO-mediated m6A modification profile in PTC cells and Apolipoprotein E (APOE) was identified as the target gene for FTO-mediated m6A modification using RNA-seq and MeRIP-seq. FTO knockdown significantly increased APOE mRNA m6A modification and upregulated its expression. FTO-mediated m6A modification of APOE mRNA was recognized and stabilized by the m6A reader IGF2BP2. The findings showed that APOE also promoted tumor growth through glycolysis in PTC. Analysis showed that FTO/APOE axis inhibits PTC glycolysis by modulating IL-6/JAK2/STAT3 signaling pathway. Conclusion: FTO acts as a tumor suppressor to inhibit tumor glycolysis in PTC. The findings of the current study showed that FTO inhibited expression of APOE through IGF2BP2-mediated m6A modification and may inhibit glycolytic metabolism in PTC by modulating IL-6/JAK2/STAT3 signaling pathway, thus abrogating tumor growth. [ABSTRACT FROM AUTHOR]

Objective: Children with papillary thyroid cancer (PTC) have a higher invasive rate and distant metastasis rate, but the mortality rate is lower with unknown reasons. The majority of PTC cases comprise classical papillary thyroid carcinoma (CPTC) and follicular variant papillary thyroid carcinoma (FVPTC). This study aimed to determine the relationship between histopathological subtype and rate of distant metastasis and investigate factors influencing distant metastasis in pediatric PTC. Methods: A total of 102,981 PTC patients were recruited from SEER registry, 2004-2015. Proportion of distant metastasis between children (≤18 years) and adults with different histopathological subtypes was compared by propensity score matching. The cut-off age for distant metastasis in children was calculated by receiver operating characteristic (ROC) curve, and the risk factors for distant metastasis in pediatric patients were analyzed by logistic regression models. Results: Among the 1,484 children and 101,497 adults included in the study, the incidence of CPTC patients with distant metastasis in children was higher than that in adults (p <0.001). The ROC curve was calculated, which yielded a cut-off age for distant metastasis in CPTC children as 16 years old. In CPTC, the proportion of young children (2-16 years) with distant metastasis was higher than that of adolescents (17-18 years) and adults (>18 years) (both p <0.001). While there was no such trend in FVPTC. In young children (2-16 years), the incidence of CPTC with distant metastasis was higher than FVPTC (p =0.006). There was no difference between the proportion of CPTC and FVPTC with distant metastasis in adolescents (17-18 years) and adults. Logistic regression models revealed that extrathyroidal extension, lymph node metastasis and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2 -16 years. Conclusions: In CPTC, the incidence of distant metastasis in young children (2-16 years) was significantly higher than that in adolescents (17-18 years) and adults (>18 years). In patients with distant metastasis aged 2-16 years, the proportion of CPTC was higer than that of FVPTC. Extrathyroidal extension, lymph node metastasis, and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2-16 years. [ABSTRACT FROM AUTHOR]

Background: As many inconsistent reports on the clinical manifestations and prognosis between unilateral unifocal PTC (UUPTC) and unilateral multifocal PTC (UMPTC), identifying the difference should guide management. The purpose of this study was to investigate other additional differences between UUPTC and UMPTC in addition to their difference in the number of cancer foci. Data Sources: A systematic literature search was conducted in the PubMed and Web of Science databases for relevant studies published before December 31, 2020. Their reference lists were also reviewed. Review Methods: Two reviewers independently extracted data and assessed the quality of eligible studies. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included. Data were analyzed using the RevMan 5.3 software. Results: Fifteen studies comprising 9,665 patients were selected for the meta-analysis. UMPTC occurred in 10% to 36% of all PTC cases. There were no significant differences between UMPTC and UUPTC patients in age, gender, tumor size, and extrathyroidal extension (ETE). However, significant differences (P < 0.05) between UMPTC and UUPTC patients were observed in central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), tumor-node-metastasis (TNM) stage I+II, TNM stage III+IV, the recurrence/persistence of the UMPTC group after total thyroidectomy and overall recurrence/persistence. Conclusion: UMPTC patients are more likely to have CLNM, LLNM, more advanced TNM stage, and recurrence/persistence than UUPTC patients. Compared with UUPTC, UMPTC patients should undergo central lymph node dissection, and pay more attention to LLNM, TNM stage and recurrence/persistence during the follow-up. [ABSTRACT FROM AUTHOR]

A qualitative study published in the journal Thyroid examined the barriers and facilitators to selecting active surveillance (AS) as a treatment strategy for low-risk papillary thyroid microcarcinoma (PTMC) in China. The study found that some patients lacked a definitive pathological diagnosis, which may influence their decision to choose AS. Additionally, not all PTMCs are suitable for AS, and patients with aggressive clinical characteristics or high risk of invasion are recommended immediate surgery. The perception of PTMC as a "good carcinoma" and the ability of clinicians to reduce patients' fear and provide detailed follow-up protocols also affect patients' choices. The authors suggest that a multidisciplinary team and good quality control are necessary for accurate diagnosis and evaluation of primary tumors considered for AS. [Extracted from the article]

NEAT1 (nuclear paraspeckle assembly transcript 1) is an oncogenic long non-coding RNA (lncRNA) that facilitates tumorigenesis in multiple cancers. In papillary thyroid cancer (PTC), the molecular mechanism by which NEAT1 affects invasion and metastasis remains elusive. RNA sequencing was used to discover differentially expressed NEAT1_2 downstream genes. Protein and RNA expression analyses and immunohistochemistry detected the expression of NEAT1_2 , Transglutaminase 2 (TGM2), and microRNA-491 (miR-491) among PTC and non-cancerous tissues. Transwell and wound healing assays, and a mouse model of lung metastasis were used for further functional analyses. Bioinformatics was performed to predict miRNAs binding to both NEAT1_2 and TGM2. Rescue experiments and dual-luciferase reporter assays were performed. In PTC tissues, NEAT1_2 expression was markedly increased and regulated TGM2 expression. TGM2 was overexpressed in PTC, correlating positively with exthyroidal extension and lymph node metastasis. TGM2 knockdown significantly inhibited invasion and metastasis. NEAT1_2 sponged miR-491, acting as a competing endogenous RNA to regulate TGM2 expression. Fibronectin 1 (FN1) was predicted as a TGM2 target. TGM2 could transcriptionally activate FN1 by promoting nuclear factor kappa B (NFκb) p65 nuclear translocation, ultimately promoting PTC invasion/metastasis. These findings identify that NEAT1_2 sponges miR-491 to regulate TGM2 expression. TGM2 activates FN1 via NFκb to promote PTC invasion and metastasis. [ABSTRACT FROM AUTHOR]

Background: As hypocalcemia is the most common complication of total thyroidectomy, identifying its risk factors should guide prevention and management. The purpose of this study was to determine the risk factors for postthyroidectomy hypocalcemia. Methods: We searched PubMed, Web of Science and EMBASE through January 31, 2019, and assessed study quality using the Newcastle–Ottawa Scale. Results: Fifty studies with 22,940 patients met the inclusion criteria, of which 24.92% (5716/22,940) had transient hypocalcemia and 1.96% (232/11,808) had permanent hypocalcemia. Significant (P < 0.05) predictors of transient hypocalcemia were: younger age, female, parathyroid autotransplantation (PA), inadvertent parathyroid excision (IPE), Graves' disease (GD), thyroid cancer, central lymph node dissection, preoperative severe Vitamin D deficiency, preoperative Vitamin D deficiency and a lower postoperative 24 h parathyroid hormone (PTH) level. Preoperative magnesium, preoperative PTH and Hashimoto's thyroiditis were not significant predictors of transient hypocalcemia. IPE, GD, and thyroid cancer were associated with an increased rate of permanent hypocalcemia, but gender and PA did not predict permanent hypocalcemia. Conclusion: Important risk factors for transient and permanent hypocalcemia were identified. However, given the limited sample size and heterogeneity of this meta-analysis, further studies are required to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are emerging regulators of a diverse range of biological processes through various mechanisms. Genome-wide association studies of tumor samples have identified several lncRNAs, which act as either oncogenes or tumor suppressors in various types of cancers. Small nucleolar RNAs (snoRNAs) are predominantly found in the nucleolus and function as guide RNAs for the processing of transcription. As the host genes of snoRNAs, lncRNA small nucleolar RNA host genes (SNHGs) have been shown to be abnormally expressed in multiple cancers and can participate in cell proliferation, tumor progression, metastasis, and chemoresistance. Here, we review the biological functions and emerging mechanisms of SNHGs involved in the development and progression of endocrine-related cancers including thyroid cancer, breast cancer, pancreatic cancer, ovarian cancer and prostate cancer. [ABSTRACT FROM AUTHOR]

Background. The current treatment for postoperative hypoparathyroidism has shortcomings, such as repeated blood monitoring for dosage adjustment, uncertain long-term efficacy, and the high price of recombinant parathyroid hormone therapy. Adipose-derived stem cells can undergo adipogenic and osteogenic differentiation in vitro and are considered a novel source of parathyroid-like cells, but the idea lacks theoretical basis and feasibility. We aimed at establishing a protocol for differentiating adipose-derived stem cells into parathyroid-like cells for treating hypoparathyroidism. Materials/Methods. Adipose-derived stem cells were isolated and purified from the inguinal adipose tissue of Sprague Dawley rats. Adipogenic differentiation and osteogenic differentiation of the cells were identified by oil red O and alizarin red S staining, respectively. The adipose-derived stem cells were stimulated by sonic hedgehog (SHH) and activin A. The differentiation of the adipose-derived stem cells to parathyroid-like cells was confirmed by the detection of parathyroid hormone and the related parathyroid markers. Results. Adipose-derived stem cells were successfully isolated and purified from the rat adipocytes. The adipogenic and osteogenic differentiation capabilities of the adipose-derived stem cells were determined. SHH and activin A stimulated parathyroid hormone secretion by the adipose-derived stem cells and significantly increased the expression of calcium-sensing receptor (CaSR), parathyroid hormone, and glial cells missing homolog 2 (GCM2) in the cells in a time- and concentration-dependent manner. Conclusion. We successfully differentiated rat adipose-derived stem cells into parathyroid-like cells, which will pave a new route to curing hypoparathyroidism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study, the types of micropores in a reservoir are analyzed using casting thin section (CTS) observation and scanning electron microscopy (SEM) experiments. The high‐pressure mercury injection (HPMI) and constant‐rate mercury injection (CRMI) experiments are performed to study the micropore structure of the reservoir. Nuclear magnetic resonance (NMR), gas‐water relative seepage, and gas‐water two‐phase displacement studies are performed to examine the seepage ability and parameters of the reservoir, and further analyses are done to confirm the controlling effects of reservoir micropore structures on seepage ability. The experimental results show that Benxi, Taiyuan, Shanxi, and Shihezi formations in the study area are typical ultra‐low porosity and ultra‐low permeability reservoirs. Owing to compaction and later diagenetic transformation, they contain few primary pores. Secondary pores are the main pore types of reservoirs in the study area. Six main types of secondary pores are: intergranular dissolved pores, intragranular dissolved pores, lithic dissolved pores, intercrystalline dissolved pores, micropores, and microfracture. The results show that reservoirs with small pore‐throat radius, medium displacement pressure, and large differences in pore‐throat structures are present in the study area. The four types of micropore structures observed are: lower displacement pressure and fine pores with medium‐fine throats, low displacement pressure and fine micropores with fine throats, medium displacement pressure and micropores with micro‐fine throats, and high displacement pressure and micropores with micro throats. The micropore structure is complex, and the reservoir seepage ability is poor in the study areas. The movable fluid saturation, range of the gas‐water two‐phase seepage zone, and displacement types are the three parameters that well represent the reservoir seepage ability. According to the characteristic parameters of microscopic pore structure and seepage characteristics, the reservoirs in the study area are classified into four types (I–IV), and types I, II, and III are the main types observed. From type I to type IV, the displacement pressure increases, and the movable fluid saturation and gas‐water two‐phase seepage zone decrease, and the displacement type changes from the reticulation‐uniform displacement to dendritic and snake like. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Little is known about annual hazard rates of cancer mortality and recurrence for papillary thyroid cancer (PTC). This study investigated the time-varying pattern of cancer death and recurrence from PTC and independent prognostic factors for cause-specific mortality (CSM) and recurrence of PTC. Methods: This retrospective chart review enrolled 466 patients diagnosed with PTC who underwent curative initial surgery between April 1981 and December 1991 with a median follow-up of 18.4 years. Clinical characteristics, cancer mortality (primary endpoint), and recurrence (secondary endpoint) were ascertained. The failure rates of either death or recurrence were estimated using the Kaplan–Meier methods, and annual death/recurrence hazard was depicted using hazard function. Results: In this Japanese cohort where only 1.5% of patients received radioactive iodine therapy, the 10-, 20-, and 30-year CSM rates were 2.7%, 6.2%, and 8.6%, respectively. Eleven (44.0%) cases of death occurred within the first 10 years, whereas 10 (40.0%) and 4 (16.0%) cases occurred within 10–20 and 20–30 years after surgery, respectively. The 10-, 20-, and 30-year recurrence rates were 11.3%, 21.8%, and 29.4%, respectively. Forty-six (54.8%) cases of recurrence occurred within the first 10 years, predominantly within the first five years (31 cases; 36.9%), whereas 29 (34.5%), 7 (8.3%), and 2 (2.4%) cases occurred within 10–20, 20–30, and ≥30 years after surgery, respectively. Age ≥55 years was the only independent prognostic factor for CSM. Age ≥55 years, male, tumor size > 4 cm, extranodal extension, and positive pathological lymph node metastasis were independent prognostic factors for recurrence. The annual hazard curve of cancer mortality presented a double-peaked distribution, with a first peak at the 10th year, and the second peak reaching the maximum at the 20th year after surgery for the entire population. The annual hazard curve of recurrence showed a triple-peaked pattern, with surges at about 12, 22, and 29 years after surgery. Conclusions: Patients with PTC harboring at least one of the prognostic characteristics may be at persistent risk of cancer mortality and recurrence even 10 or more years after initial treatment. Understanding the hazard rate of PTC is key to creating more tailored treatment and surveillance. [ABSTRACT FROM AUTHOR]

Background: The incidence of papillary thyroid cancer (PTC) is increasing faster than any other solid tumors worldwide. Invasion and metastasis are the main reasons for the poor prognosis of patients with PTC. Previously, we observed significantly low expression of miRNA-299-5p in invasive PTC tissue samples. Aim: The present study aimed to determine whether miR-299-5p plays a key role in PTC migration and invasion. Materials and methods: The miR-299-5p expression level was measured using quantitative real-time PCR in 109 human PTC samples and paired adjacent normal tissues and in the human BCPAP PTC cell line. The effects of miR-299-5p on PTC cell migration and invasion were assessed using wound healing and transwell assays. In addition, we searched for the miR-299-5p target, and the potential mechanism was demonstrated using a reporter assay and rescue experiment. Results: The expression of miR-299-5p was associated with gender and extrathyroidal extension, and an elevated level of miR-299-5p suppressed BCPAP cell migration and invasion. Estrogen receptor α (ERα) is a direct target of miR-299-5p. The expression level of ERα was significantly higher in PTC tissues and was associated with migration and invasion in PTC cells. Overexpression of ERα could impair miR-299-5p-induced inhibition of migration and invasion. As a key factor of the pathway related to PTC invasion, Gli1 can be combined with ERα and can be regulated by miR-299-5p. Conclusion: Our data suggested that miR-299-5p could participate in PTC migration and invasion and could be a potential therapeutic target for patients with aggressive PTC tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The long non-coding RNA GAS8 antisense RNA 1 (lncRNA GAS8-AS1) is a tumor suppressor in papillary thyroid cancer (PTC), but the mechanisms underlying how GAS8-AS1 regulates PTC biology remain unclear. Here, we evaluated the molecular function of GAS8-AS1 in regulating autophagy in PTC cell lines.Methods: GAS8-AS1 was overexpressed and knocked down in PTC cell lines by transfecting with expression plasmids or short interfering RNAs (siRNAs). Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8). qRT-PCR and western blot were used to determine changes in expression of autophagy-related genes. Autophagy was evaluated by immunofluorescence and transmission electron microscopy.Results: Relative GAS8-AS1 expression was lower in the PTC cell lines, TPC1 and BCPAP, compared to a normal thyroid cell line. Overexpression of GAS8-AS1 inhibited proliferation, significantly increased the ratio of LC3-II/LC3-I, and reduced p62 expression, whereas GAS8-AS1 knockdown demonstrated opposite effects. In GAS8-AS1 overexpressing cell lines, LC3 immunofluorescence staining demonstrated increased punctate aggregates of LC3 staining, and transmission electron microscopy revealed increased numbers of autophagosomes. Autophagy-related gene 5 (ATG5) was markedly upregulated by GAS8-AS1 overexpression and downregulated by GAS8-AS1 knockdown. Finally, silencing of ATG5 attenuated autophagy activation and rescued the inhibition of cell proliferation caused by GAS8-AS1.Conclusions: In PTC cell lines, GAS8-AS1 inhibited proliferation, activated autophagy, and increased ATG5 expression. Downregulation of ATG5 reversed GAS8-AS1-mediated activation of autophagy leading to cell death, revealing a novel mechanism of the GAS8-AS1-ATG5 axis in PTC cell lines. This provided a new experimental basis to explore the effects of lncRNA on autophagy in the treatment of thyroid cancer. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC), the most common histological subtype of thyroid cancer, accounts for between 80 and 90% of all thyroid cancer cases. Previous studies have suggested that microRNAs (miRNAs/miRs) are involved in the development of PTC. The aim of the present study was to investigate whether miR-144 inhibits cellular proliferation in PTC. The expression of miR-144 was detected in PTC and corresponding adjacent non-cancerous tissues, and in the PTC cell line IHH4, using reverse transcription-quantitative polymerase chain reaction. Associations between miR-144 expression levels and the clinicopathological characteristics were analyzed. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of miR-144 expression, and the potential function of miR-144 was investigated in IHH4 cells using a Cell Counting Kit-8 and colony formation assays. Western blotting was applied to analyze the expression level of WW domain-containing transcription regulator 1 (WWTR1) in PTC tissues. miR-144 was significantly downregulated in PTC tissues and the PTC cell line. Low expression of miR-144 was associated with larger tumor sizes (P<0.001). The ROC curves demonstrated that miR-144 may be a potential biomarker for identifying PTC and non-cancerous diseases (sensitivity, 58.7%; speci- ficity, 87.3%) as well as to differentiate PTC with tumor sizes ≥2 cm (sensitivity, 79.2%; specificity, 69.2%). Upregulation of miR-144 significantly suppressed proliferation in IHH4 cells. WWTR1 was overexpressed in PTC tissues compared with in adjacent non-cancerous tissues, and the ectopic expression of miR-144 downregulated WWTR1 in IHH4 cells. Co-transfection with pcDNA-WWTR1 and miR-144 'rescued' the proliferation inhibition. The results of the present study collectively demonstrated that miR-144 is downregulated in PTC, that low expression levels of miR-144 are associated with larger tumor sizes and that miR-144 inhibits cellular proliferation in PTC by targeting WWTR1. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Current evidence suggests that the human genome produces a large number of non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs). Generally, lncRNAs are defined as RNA transcripts longer than 200 nucleotides that are not transcribed into proteins. In recent years, lncRNAs have been reported to play oncogenic roles in tumourigenesis. However, minimal research has been performed on the expression and clinicopathological significance of lncRNAs in papillary thyroid cancer (PTC). In the present study, we investigated not only the expression and clinicopathological significance of a novel lncRNA, NR_036575.1, in PTC tissues and adjacent non-cancerous tissues but also its potential function in TPC1 cells. The expression levels of the lncRNA NR_036575.1 in 83 pairs of PTC tissues and adjacent non-cancerous tissues were detected via quantitative real-time polymerase chain reaction. The relationships between the expression levels and clinicopathological characteristics of the lncRNA NR_036575.1 were analysed. In addition, we established two receiver operating characteristic (ROC) curves to assess the diagnostic value of NR_036575.1 expression. Cell Counting Kit-8 and transwell assays were used to assess cell proliferation and migration, respectively. The expression levels of the lncRNA NR_036575.1 were significantly higher in PTC tissues than in adjacent non-cancerous tissues. High NR_036575.1 expression was associated with extrathyroidal extension (ETE) ( P = 0.011) and tumour size ( P = 0.006). The ROC curves indicated that NR_036575.1 could potentially serve as a biomarker for identifying PTC and related, non-cancerous diseases (sensitivity, 80.7 %; specificity, 88 %), as well as for differentiating between PTC with or without ETE (sensitivity, 57.8 %; specificity, 86.7 %). NR_036575.1 knock-down significantly inhibited the proliferation and migration of TPC1 cells. Our findings are the first to describe lncRNA NR_036575.1 overexpression in PTC. NR_036575.1 expression was associated with both ETE and tumour size. In addition, NR_036575.1 modulation could regulate TPC1 cell proliferation and migration. The results of our study suggest that NR_036575.1 could be applied as a potential biomarker and a novel therapeutic target for PTC patients. [ABSTRACT FROM AUTHOR]

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 (TGFβ1) was the direct target of miR-663 and mediated the effect of miR-663 on PTC development. By targeting TGFβ1, 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 TGFβ1 and regulate EMT progress of PTC cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Whether central lymph node metastasis is a reliable indicator of lateral lymph node metastasis in papillary thyroid carcinoma remains obscure. To investigate the value of central lymph node metastasis for predicting lateral compartment involvement, we performed a meta-analysis of published studies.Data Sources: A systematic literature search of PubMed, EMBASE, and Chinese National Knowledge Infrastructure databases was completed, and the reference lists of the identified articles and prior relevant reviews were examined.Review Methods: Two reviewers extracted data and assessed the quality of eligible studies independently. Odds ratios and 95% confidence intervals were pooled through a random effects meta-analysis model.Results: Twenty-one studies were eligible and further analyzed in this meta-analysis. The risk of lateral lymph node metastasis was significantly higher in the central lymph node-positive group than in the negative group (odds ratio = 7.64, 95% confidence interval: 5.59-10.44), with moderate heterogeneity across studies (P = .007, I(2) = 48.6%). Subgroup analyses and sensitivity analysis suggested that the results were consistent and credible. However, Begg's funnel plot and Egger linear regression test revealed a likelihood of publication bias (P = .000).Conclusion: This meta-analysis suggests that central lymph node metastasis is valuable for predicting lateral compartment involvement in patients with papillary thyroid carcinoma. For those patients with central lymph node metastasis, additional attention should be paid to the lateral neck, as the risk of lateral lymph node metastasis was significantly higher in the central lymph node-positive group than in the negative group. Further studies regarding appropriate management for patients with high risk of lateral involvement are needed. [ABSTRACT FROM AUTHOR]

Background: Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically negative central compartment lymph nodes (CN0) remains controversial. The phrase “clinically negative” is used to indicate that patients exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized tomography (CT) preoperatively. In this study, we analyze the risk factors for CLNM in CN0 patients. Methods: The PUBMED and SCIE databases were systematically searched for works published through January 31, 2015. All of the patients included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was used to analyze the data. Results: Twenty studies and 9084 patients were included in this meta-analysis. The following variables were associated with an increased risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42–1.78, p<0.00001), male sex (OR = 1.95, 95% CI = 1.63–2.32, p<0.00001), multifocality (OR = 1.43, 95% CI = 1.22–1.67, p<0.00001), tumor size > 2 cm for PTC patients (OR = 2.98, 95% CI 2.08–4.28, p<0.00001) or tumor size > 0.5 cm for papillary thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71–3.09, p<0.00001), location of the primary tumor in the central area and low pole (OR = 1.86, 95% CI = 1.48–2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI = 2.24–8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76–2.94, p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39–2.41, p<0.00001). PTC (tumor size>1cm) exhibited a higher risk factor associated with CLNM than PTMC (tumor size<1cm) (OR = 2.83, 95% CI = 2.15–3.72, p<0.00001). Bilateral tumors (OR = 1.21, 95% CI = 0.92–1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88, 95% CI = 0.71–1.09, p = 0.25) had no association with CLNM in CN0 patients. Conclusions: Our systematic review identified several clinical features associated with CLNM in CN0 patients, including age, sex, multifocality, size, location, lymphovascular invasion, capsular invasion, and extrathyroidal extension. These factors should guide the application of PCLND in CN0 patients. [ABSTRACT FROM AUTHOR]

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 β1 (wild-type ERβ), 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 ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 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 ERβ1 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 ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 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 ERβ1 has some inhibitory actions. [ABSTRACT FROM AUTHOR]