The effects of iodine 131 treatment on chromosomal and oxidative DNA damage in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy.

Plasma miRNA-146b-3p, -222-3p, -221-5p, -21a-3p Expression Levels and TSHR Methylation: Diagnostic Potential and Association with Clinical and Pathological Features in Papillary Thyroid Cancer.

This study aimed to investigate the expression of microRNAs (miRNAs) -146b-3p, -221-5p, -222-3p, and -21a-3p and the methylation pattern of the thyroid-stimulating hormone receptor (TSHR) gene in blood plasma samples from papillary thyroid cancer (PTC) patients before and after thyroidectomy compared to healthy controls (HCs). This study included 103 participants, 46 PTC patients and 57 HCs, matched for gender and age. Significantly higher preoperative expression levels of miRNAs and TSHR methylation were determined in the PTC patients compared to HCs. Post-surgery, there was a notable decrease in these biomarkers. Elevated TSHR methylation was linked to larger tumor sizes and lymphovascular invasion, while increased miRNA-222-3p levels correlated with multifocality. Receiver operating characteristic (ROC) analysis showed AUCs below 0.8 for all candidate biomarkers. However, significant changes in the expression of all analyzed miRNAs and TSHR methylation levels indicate their potential to differentiate PTC patients from healthy individuals. These findings suggest that miRNAs and TSHR methylation levels may serve as candidate biomarkers for early diagnosis and monitoring of PTC, with the potential to distinguish PTC patients from healthy individuals. Further research is needed to validate these biomarkers for clinical application.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. METHODS: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. RESULTS: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001. CONCLUSION: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.

Long-Term Changes of Urinary Exosomal Peptide Levels After Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational Study.

Background: The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Methods: Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. Results: A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Conclusion: Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. Trial Registration: ClinicalTrials.gov: NCT03488134.

Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

Analyzing circulating tumor cells and epithelial-mesenchymal transition status of papillary thyroid carcinoma patients following thyroidectomy: a prospective cohort study.

BACKGROUND: This study investigated the prevalence and subtype distribution of circulating tumor cells (CTCs) in patients with papillary thyroid cancer (PTC) before and after thyroidectomy to determine the potential of CTC count as a noninvasive marker of the efficacy of surgical treatment in PTC. MATERIALS AND METHODS: Between January 2021 and January 2022, 62 PTC patients who underwent thyroidectomy at Seoul National University Bundang Hospital were prospectively evaluated. Peripheral blood samples (7.5 ml) were collected from each patient for CTC analysis before surgery and at 2 weeks and 3 months after surgery. CTC count and the distribution of CTC subtypes, including epithelial, epithelial-mesenchymal, and mesenchymal phenotypes, were analyzed using the negative selection method and immunofluorescence staining. The relationship between CTC count and clinicopathological characteristics was analyzed before and after surgery. RESULTS: Before surgery, CTCs were detected in 87% (54/62) of patients; the mean CTC count was 8.0 and the median was 5.0 in 7.5 ml of peripheral blood. The mesenchymal or epithelial-mesenchymal phenotypes were predominant. After thyroidectomy, the mean and median CTC count values decreased to 5.3 and 2.5, respectively, at 2 weeks and to 4.3 and 3.0, respectively, at 3 months. This postoperative reduction in CTCs was more pronounced in patients with lymphatic invasion, lymph node metastasis, or BRAF V600E mutation. CONCLUSION: CTCs were detected in patients with PTC with a predominance of cells undergoing epithelial-mesenchymal transition. The CTC count decreased postoperatively, suggesting that liquid biopsy with CTC detection could be a valuable noninvasive tool for monitoring the efficacy of surgery in PTC.

The impact of intraoperative neural monitoring during papillary thyroid cancer surgery on completeness of thyroidectomy and thyroglobulin response: a propensity-score matched study.

BACKGROUND: Intraoperative neural monitoring (IONM) has been utilized for a variety of thyroid pathologies, including papillary thyroid carcinoma (PTC). Remnant thyroid tissue following total thyroidectomy (TT) in patients with PTC is associated with increased recurrence. The aim of this study is to investigate whether the use of IONM in PTC surgery has an impact on the completeness of thyroidectomy. METHODS: Retrospectively, patients with preoperative diagnosis of PTC, who underwent TT in a tertiary center were reviewed. They were grouped based on the IONM usage, and 1:1 propensity-score match was performed. Primary outcome was the completeness of thyroidectomy, determined by measuring postoperative stimulated thyroglobulin levels (sTg). RESULTS: Among 274 clinically node-negative PTC patients who underwent TT and ipsilateral prophylactic central lymph-node dissection, a total of 170 patients (85:85) were matched. Postoperative sTg levels were significantly lower in the IONM group (1 ng/dL vs. 0.4 ng/dL; p < 0.01) with higher percentage of the patients with sTg levels <1 ng/ml (50.6% vs. 69.4%; p = 0.01). More patients in the no-IONM group received RAI ablation with significantly higher doses (mean mci: 120 vs. 102; p = 0.02). CONCLUSION: The use of IONM during thyroidectomy provides improvement in the completeness of thyroidectomy and reduction in postoperative sTg levels which can be used as a guide by clinicians to avoid RAI ablation in selected PTC patients and to adjust low ablative doses in patients who are scheduled for remnant ablation.

Enhancing Angioinvasion Assessment in Papillary Thyroid Cancer Via a Biomarker Panel Involving TAC, 8-OHdG, and Sortilin.

CONTEXT: Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and prognosis. OBJECTIVE: This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity, total antioxidant capacity [TAC], and sortilin), as potential indicators of angioinvasion in PTC. DESIGN: A cross-sectional study involving 50 angioinvasive patients with PTC (study group) and 30 patients with PTC with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion. SETTING: Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context. PATIENTS OR OTHER PARTICIPANTS: Participants included patients with PTC, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded. INTERVENTION(S): Serum biomarkers were measured to evaluate their association with PTC angioinvasion. MAIN OUTCOME MEASURE(S): Primary outcome measures included serum levels of 8-OHdG, total oxidative capacity, TAC, and sortilin. RESULTS: Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, whereas TAC showed a notable decrease (all P < .01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high area under the curve value (0.963) for angioinvasion discernment. CONCLUSION: Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results.

Comparison of pathophysiology in subclinical hyperthyroidism with different etiologies.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

The relationship between papillary thyroid cancer and triglyceride/glucose index, which is an indicator of insulin resistance.

OBJECTIVE: The incidence of thyroid cancer and metabolic syndrome has been increasing at the same rate over the past few decades. We hypothesized that there would be a direct relationship between thyroid papillary cancer and triglyceride/glucose index (TyG). PATIENTS AND METHODS: A total of 382 operated patients were divided into two groups: patients operated on for papillary thyroid cancer and for non-malignant reasons. Each patient's age, gender, operation times, presence of neck dissection, serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), fasting blood glucose and triglyceride levels were scanned retrospectively from the archive system. RESULTS: TyG index was statistically higher in the malignant group. Receiver operating characteristic (ROC) curves obtained for TyG levels at the time of diagnosis of thyroid papillary cancer were AUC: 0.608. The threshold value for TyG was 6,252. The sensitivity of this value was 62.8% and the specificity was 49.2%. CONCLUSIONS: In this study, we investigated the predictive effect of the TyG index in differentiating thyroid papillary carcinoma from non-malignant thyroid lesions. We concluded that the TgY index can be used to identify people at high risk of thyroid papillary cancer and to plan treatment.

Preoperative platelet distribution width-to-platelet ratio combined with serum thyroglobulin may be objective and popularizable indicators in predicting papillary thyroid carcinoma.

OBJECTIVES: The incidence of papillary thyroid carcinoma (PTC) has increased more rapidly than that of any other cancer type in China. Early indicators with high sensitivity and specificity during diagnosis are required. To date, there has been a paucity of studies investigating the relationship between preoperative platelet distribution width-to-platelet count ratio (PPR) and PTC. This study thus aimed to assess the diagnostic value of PPR combined with serum thyroglobulin (Tg) in patients with PTC. METHODS: A total of 1001 participants were included in our study. 876 patients who underwent surgery for nodular goiter were divided into the PTC group or benign thyroid nodule (BTN) group according to pathology reports, and 125 healthy controls (HCs) were included. Preoperative hemogram parameters and serum Tg levels were compared among three groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of PPR combined with serum Tg for diagnosing PTC. RESULTS: Platelet distribution width (PDW) and PPR levels were higher in the PTC group than in the BTN and HC groups (both p < 0.05) but did not significantly differ between the BTN and HC groups. PDW and PPR levels significantly differed in the presence/absence of lymph node metastasis, the presence/absence of capsule invasion (p = 0.005), and TNM stages (p < 0.001). Multivariable analyses indicated that high serum Tg levels [adjusted odds ratio (OR), 1.007; 95% confidence interval (CI), 1.004-1.009; p < 0.001], high neutrophil-to-lymphocyte ratio (NLR,adjusted OR, 1.928; 95% CI, 1.619-2.295; p < 0.001), and high PPR (adjusted OR, 1.378; 95% CI, 1.268-1.497; p < 0.001) were independent risk factors for PTC. In ROC analysis, the areas under the curves (AUCs) of serum Tg, PDW, PPR, and NLR for predicting PTC were 0.603, 0.610, 0.706, and 0.685, respectively. PPR combined with serum Tg (PPR + Tg) had a higher diagnostic value (AUC, 0.738; sensitivity, 60%; specificity, 74.7%) compared with PDW + Tg (AUC, 0.656; sensitivity, 64.4%; specificity, 59.9%) and NLR + Tg (AUC, 0.714; sensitivity, 61.6%; specificity, 71.1%). CONCLUSIONS: Preoperative PPR combined with serum Tg may be objective and popularizable indicators for effective predicting PTC.

In Situ Preservation of Parathyroid Gland With Vasculature for Papillary Thyroid Carcinoma Is Associated With Higher PTH Levels After Total Thyroidectomy.

PURPOSE: To evaluate the impact of parathyroid gland vasculature preservation in-situ technique (PGVPIST) on postoperative parathyroid hormone (PTH) and calcium plasma levels in thyroid patients undergoing total thyroidectomy for papillary thyroid carcinoma (PTC). STUDY DESIGN: Retrospective cohort study. METHODS: Patients with PTC who underwent total thyroidectomy by either the conventional technique (group 1, January 2019 to January 2020) or PGVPIST (group 2, January 2020 to January 2021) were compared. Postoperative blood calcium levels and PTH levels were assessed in these groups. RESULTS: Totally 149 patients with consecutive PTC underwent total thyroidectomy, including 60 patients in group 1 and 89 patients in group 2. Postoperative serum calcium levels in group 1 were insignificantly lower than in group 2 at day 1 (2.18 ± 0.02 vs 2.15 ± 0.01 mmol/L) and day 30 (2.27 ± 0.02 vs 2.38 ± 0.11) after surgery. But postoperative serum PTH levels in group 1 were significantly lower than that in group 2 at day 1 (23.68 ± 2.54 vs 31.46 ± 2.11 pg/mL) and day 30 (45.63 ± 3.21 vs 55.65 ± 2.89 pg/mL) after surgery. CONCLUSION: Parathyroid gland vasculature preservation in-situ technique for PTC is associated with higher PTH level after total thyroidectomy. The parathyroid gland vasculature mostly strongly adheres with adjacent thyroid parenchyma. Therefore, deferred processing of tiny thyroid parenchyma of parathyroid gland vessels is essential to prevent devascularization.

Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis.

Circular RNAs (circRNAs) or exosomes have been reported to exert key regulatory and/or communication functions in human cancer. Nevertheless, current literature on the effects of exosomal circRNAs on tumor invasion and metastasis in thyroid cancer is incomplete. The role of tumor-derived exosomes in driving in vitro papillary thyroid carcinoma (PTC) progression and metastasis requires further investigation. In our study, Exosomes were harvested from PTC patient serum and PTC cell culture medium. Gene expression analysis in PTC cell lines and exosomes was performed with quantitative reverse-transcription polymerase chain reaction. Transwell, wound healing, Western blot assays, and the cell counting kit-8 were applied for functional analysis. Dual-luciferase reporter assay was used to examine the interaction between hsa_circ_007293 (circ007293), microRNA (miR)-653-5p, and paired box 6 (PAX6). Results showed that circ007293 was enriched in exosomes derived from PTC patient serum and cell culture media. Moreover, circ007293 could enter PTC cells through exosomes, and exosomal circ007293 promoted PTC cell epithelial-mesenchymal transition, invasion, migration, and proliferation. circ007293 knockdown reversed the malignant phenotype of PTC cells in vitro. Additionally, circ007293 could competitively bind with miR-653-5p to regulate PAX6 expression. Notably, miR-653-5p overexpression or PAX6 inhibition suppressed the malignant effects of exosomal circ007293. These results evidenced that exosomal circ007293 induced EMT and augmented the invasive and migratory abilities of PTC cells via the miR-653-5p/PAX6 axis, suggesting that it may serve as a promising biomarker for cancer progression.

Preoperative thyroid-stimulating hormone associated risk of differentiated thyroid cancer in patients with thyroid nodules.

In an assessment of risk for differentiated thyroid cancer (DTC) in individuals with human papillary thyroid cancer (PTC) and thyroid nodules a cohort prospective study was undertaken to establish the significance of preoperative thyroid-stimulating hormone (TSH) levels. Confirmed histologically PTC cases in one tertiary care center, and matched healthy individuals were tested for TSH, T3, T4 and T4 free total. The ORs and 95% confidence intervals have been calculated using conditional logistic regression models (CI). The blood TSH levels were related to the higher risk of PTC for men (OR,0,09; 95% Ci, 04-0,21, 95% CI and women) compared with the middle tertile of the TSH levels in the normal range (OR,0,07; 95 percent CI, 0,04-0,1). Over the normal range of TSH levels, an elevated PTC risks were connected amongst women (OR 0,09; 95% CI, 0,04-0,21) but not amongst men (OR,0,07; 95% CI, 0,04-0,1). With an increase in TSH level in the normal range between men and women, the risk for PTC reduced (Ptrend=0.041 and 0.0001). The risk of PTC related to TSH levels has been dramatically elevated above  the normal range for men  and TSH values below the normal range for women.

Complement C4-A and Plasminogen as Potential Biomarkers for Prediction of Papillary Thyroid Carcinoma.

Background: Early diagnosis and therapy of papillary thyroid carcinoma (PTC) is essential for reducing recurrence and improving the long-term survival. In this study, we aimed to investigate the proteome profile of plasma and screen unique proteins which could be used as a biomarker for predicting PTC. Methods: Serum samples were collected from 29 PTC patients and 29 nodular goiter (NG) patients. Five PTC serum samples and five NG serum samples were selected for proteome profiles by proteomics. Eight proteins in PTC and NG serum samples were selected for confirmation by enzyme-linked immunosorbent assay analysis. Receiver operating characteristic curves was used to evaluate the diagnostic value of potential biomarkers. Results: Complement C4-A (C4A) and plasminogen (PLG) were significantly lower in serum samples of PTC patients compared with NG patients. C4A was observed to have excellent diagnostic accuracy for PTC, with a sensitivity of 91.67% and specificity of 83.33%. The diagnostic value of PLG for PTC was demonstrated by a sensitivity at 87.50% and specificity at 75.00%. The AUC for C4A and PLG was 0.97 ± 0.02 and 0.89 ± 0.05. Conclusion: C4A and PLG appeared to be excellent potential biomarkers for the prediction of PTC.

Evaluation the Presence of SERPINA5 (Exon 3) and FTO rs9939609 Polymorphisms in Papillary Thyroid Cancer Patients.

BACKGROUND: A few researches evaluated the association of polymorphisms at SERPINA5 and fat mass and obesity-associated protein (FTO) genes with papillary thyroid cancer (PTC) globally. Here, we examined the presence of genetic variations within coding exon 3 of SERPINA5 gene and FTO rs9939609 polymorphism in Iranian PTC patients. METHODS: A total of 122 patients (42 cases for SERPINA5 and 80 cases for FTO gene) and 120 healthy subjects (40 subjects or SERPINA5 and 80 subjects for FTO gene) were recruited. The genetic variation within coding exon 3 of SERPINA5 gene was evaluated by reaction-single-strand conformation polymorphism (PCR-SSCP) and FTO rs9939609 polymorphism was evaluated by RFLP-PCR assay. RESULTS: The PCR-SSCP technique detected two rs6115G>A and rs6112T>C genetic variations within coding exon 3 of SERPINA5 gene and approved also by direct sequencing. For rs6112T>C polymorphism seven patients was heterozygous and for rs6115G>A seven PTC patients were heterozygous and two patients were homozygous. CONCLUSION: This study indicated that SERPINA5 rs6115G>A and rs6112T>C polymorphisms might be a novel susceptibility locus for PTC in Iranian patients. However, our findings do not support an association between FTO rs9939609 polymorphism and PTC risk.

The diagnostic value of thyroglobulin in fine-needle aspiration of metastatic lymph nodes in patients with papillary thyroid cancer and its influential factors.

Thyroglobulin (Tg) measurement in fine-needle aspiration (FNA-Tg) has proved to be an excellent tool to identify metastatic cervical lymph nodes (CLN) before or after surgery for papillary thyroid cancer (PTC). The diagnostic value of FNA-Tg for metastatic CLN in PTC patients is higher than that of ultrasound (US) and fine-needle aspiration cytology (FNAC), especially for small or cystic LN. The combination of FNAC and FNA-Tg can provide nearly 100% diagnostic sensitivity and specificity for CLN metastasis. However, the cutoff values of FNA-Tg for metastatic CLN have not been standardized, and the reported cutoff values of FNA-Tg range from 0.2 ng/ml to 77 ng/ml because of the differences in study samples, Tg measurement methods, Tg assays kits, etc. Serum anti-thyroglobulin antibody level, serum thyroglobulin level, the presence or absence of thyroid glands, and the characteristics of CLN may be factors affecting the accuracy of FNA-Tg. This review summarizes the recent research on the application of FNA-Tg in the diagnosis of metastatic LN in PTC and provides a reliable basis for the clinical diagnosis of cervical lymph node metastasis.