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Background: Accurate preoperative prediction of cervical lymph node metastasis (LNM) for papillary thyroid carcinoma (PTC) patients is essential for disease staging and individualized treatment planning, which can improve prognosis and facilitate better management. Purpose: To establish a fully automated deep learning‐enabled model (FADLM) for automated tumor segmentation and cervical LNM prediction in PTC using ultrasound (US) video keyframes. Methods: The bicentral study retrospective enrolled 518 PTC patients, who were then randomly divided into the training (Hospital 1, n = 340), internal test (Hospital 1, n = 83), and external test cohorts (Hospital 2, n = 95). The FADLM integrated mask region‐based convolutional neural network (Mask R‐CNN) for automatic thyroid primary tumor segmentation and ResNet34 with Bayes strategy for cervical LNM diagnosis. A radiomics model (RM) using the same automated segmentation method, a traditional radiomics model (TRM) using manual segmentation, and a clinical‐semantic model (CSM) were developed for comparison. The dice similarity coefficient (DSC) was used to evaluate segmentation performance. The prediction performance of the models was validated in terms of discrimination and clinical utility with the area under the receiver operator characteristic curve (AUC), heatmap analysis, and decision curve analysis (DCA). The comparison of the predictive performance among different models was conducted by DeLong test. The performances of two radiologists compared with FADLM and the diagnostic augmentation with FADLM's assistance were analyzed in terms of accuracy, sensitivity and specificity using McNemar's x2 test. The p‐value less than 0.05 was defined as a statistically significant difference. The Benjamini‐Hochberg procedure was applied for multiple comparisons to deal with Type I error. Results: The FADLM yielded promising segmentation results in training (DSC: 0.88 ± 0.23), internal test (DSC: 0.88 ± 0.23), and external test cohorts (DSC: 0.85 ± 0.24). The AUCs of FADLM for cervical LNM prediction were 0.78 (95% CI: 0.73, 0.83), 0.83 (95% CI: 0.74, 0.92), and 0.83 (95% CI: 0.75, 0.92), respectively. It all significantly outperformed the RM (AUCs: 0.78 vs. 0.72; 0.83 vs. 0.65; 0.83 vs. 0.68, all adjusted p‐values < 0.05) and CSM (AUCs: 0.78 vs. 0.71; 0.83 vs. 0.62; 0.83 vs. 0.68, all adjusted p‐values < 0.05) across the three cohorts. The RM offered similar performance to that of TRM (AUCs: 0.61 vs. 0.63, adjusted p‐value = 0.60) while significantly reducing the segmentation time (3.3 ± 3.8 vs. 14.1 ± 4.2 s, p‐value < 0.001). Under the assistance of FADLM, the accuracies of junior and senior radiologists were improved by 18% and 15% (all adjusted p‐values < 0.05) and the sensitivities by 25% and 21% (all adjusted p‐values < 0.05) in the external test cohort. Conclusion: The FADLM with elaborately designed automated strategy using US video keyframes holds good potential to provide an efficient and consistent prediction of cervical LNM in PTC. The FADLM displays superior performance to RM, CSM, and radiologists with promising efficacy. [ABSTRACT FROM AUTHOR]

Although CCL17 has been reported to exert a vital role in many cancers, the related studies in the thyroid carcinoma have never reported. As a chemokine, CCL17 plays a positive role by promoting the infiltration of immune cells into the tumor microenviroment (TME) to influence tumor invasion and metastasis. Therefore, this study is aimed to investigate the association of CCL17 level with potential prognostic value on tumor immunity in the thyroid carcinoma (THCA) based on the bioinformatics analysis. GEPIA database was applied to analyze CCL17 mRNA expression in THCA data from TCGA database. Through the collection of the data, totally 500 tumor and 57 normal tissue samples were taken for the study. According to survival status and survival time in 500 tumor samples and CCL17 expression from RNA-seq data, all patients were categorized as high- expression (n = 64) and low-expression (n = 436) groups using X-tile program. Next, the association of CCL17 with survival in the thyroid carcinoma patients was examined by using the Kaplan–Meier plotter database. Then, weighted gene co-expression network (WGCNA) was employed to analyze the 1424 DEGs to classify 9 modules. Besides, STRING database was used to obtain the hub genes. GO and KEGG database were employed to explore blue module genes enrichment situations. In addition, TISIDB was used to analyze the relationship of CCL17 expression with tumor-infiltrating lymphocytes proportion, immunostimulators, and major histocompatibility complexes in THCA. The correlation of CCL17 with 22 TIIC subtypes was evaluated by ESTIMATE and CIBERSORT databases. The association of CCL17 level with gene marker of immune cells in THCA was analyzed by GEPIA and TIMER databases. Finally, immunohistochemistry was applied to validate CCL17 expression in 21 tumor and para-carcinoma tissue samples. CCL17 expression in tumors was significantly up-regulated relative to non-carcinoma samples. Patients from CCL17 high-expression group had significantly decreased overall survival compared with low-expression group, which has a significantly importantly potential prognostic value. Moreover, CCL17 and clinical characteristics were analyzed, suggesting that CCL17 expression significantly increased among patients of advanced stage, with advanced T classification, advanced N classification, and higher CCR4 expression. Based on WGCNA, expression of 1424 DEGs in blue module with 258 genes was negatively related to dismal survival and clinical lymph node metastasis in THCA patients. Moreover, CCR4 and CCL17 genes were identified as hub genes within blue module. CCL17 high-expression had greater ImmuneScore, StromalScore and ESTIMATEScore, while lower TumorPurity compared to the CCL17 low-expression. Then, GO and KEGG database were used to analyze blue module genes enrichment situations. The result showed that genes in blue module were associated with cytokine–cytokine receptor interaction, chemokine, and PI3K − Akt pathways. The results of tumor-infiltrating lymphocytes proportion, immunostimulators, and major histocompatibility complexes were significantly positive in CCL17 high-expression. Our findings showed that B cells naïve, T cells CD4 memory resting, T cells CD8, T cells regulatory (Tregs), and dendritic cells resting were the main immune components of THCA tumor microenvironment (TME). CCL17 high-expression in TC was significantly positively related to expression of immune cell gene markers. The result of immunohistochemistry demonstrated that CCL17 expression in tumor tissues significantly increased compared with para-carcinoma tissues. CCL17 high-expression was significantly positively associated with age and advanced N classification, suggesting that CCL17 could accelerate tumor progression by promoting the lymph node metastasis. CCL17 high-expression in THCA tumor microenvironment (TME) accelerates local infiltration of immune cells and enhances anticancer immunity, resulting in worse survival of patients and exerting potential prognostic value on tumor immunity in THCA. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the common malignancy of the endocrine system. Thyroid neoplasms are usually asymptomatic and slow growing. Uncommonly, aggressive thyroid neoplasms may invade adjacent blood vessels. Internal jugular vein invasion is a rare complication of an aggressive thyroid malignancy. Careful sonographic examination of a thrombus-like structure inside a blood vessel adjacent to the affected thyroid could reveal that the "thrombus" is part of the thyroid mass. The continuity of a thyroid neoplasm into the vascular lumen and inner-"thrombus" vascularity confirms the cancerous invasion. Ultrasound-guided fine-needle aspiration biopsy is standard for differentiating benign versus malignant thyroid nodules. Genetic testing of thyroid nodules provides valuable clinical information in addition to the routine cytological analysis. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether ultrasound-guided radiofrequency ablation (RFA) is reliable for unifocal T1aN0M0 papillary thyroid carcinoma in the isthmus (PTCI).Methods 431 patients who underwent ultrasound-guided RFA for unifocal T1aN0M0 papillary thyroid carcinoma (PTC) were divided by location of the lesion into the PTCI group (52 females, 7 males, mean age 43.79 ± 12.04 years, range 22-74 years) and the PTCL group ((291 females, 81 males, mean age 43.42 ± 10.87 years, range 18-75 years) for comparative analysis. The efficacy of ultrasound-guided RFA was evaluated by volume reduction rate (VRR), complete disappearance rate (CDR) and disease progression, and the safety was evaluated by incidence of complications.Results The two groups exhibited a consistent trend of change, with the PTCI group performing better in volume, VRR and CDR at all follow-up time points expect 1 month, but the differences were not statistically significant (p > 0.05). The mean initial volume of the PTCI group vs the PTCL group decreased significantly from 65.4 ± 69.79 vs 86.38 ± 87.09 mm³ (range 10.92-427.58 vs 3.05-471.6 mm³) to 0 vs 0 mm³ at a mean follow-up time of 31.12 ± 12.5 months (range 12-60 months); their VRR increased significantly from −618.62 ± 655.61% vs −789.85 ± 1135.07% at 1 month to 100% vs 100% at 48 months. No disease progression was found in the two groups. The PTCI group had no complications, whereas the PTCL group had a total of 7 complications (1.88%).Conclusions Ultrasound-guided RFA is reliable for unifocal T1aN0M0 PTCI. It can be promoted as an alternative to immediate surgery for selected PTC patients.

Aim This study aimed to demonstrate the role of Epstein-Barr Virus (EBV) in papillary thyroid carcinomas (PTC) developing on the background of Hashimotoʼs thyroiditis (HT). Methods The presence of EBV in tumoral tissue, lymphocytes, and peritumoral normal thyroid tissue was investigated using the in situ hybridization method in paraffin blocks. The subtypes of PTC, tumor diameter, TNM stage, multifocality, invasion of thyroid capsule, perineural invasion, and muscular tissue invasion were identified and compared according to EBV involvement. Results Eighty-one patients with HT diagnosis, with 93.8% (n=76) female and 6.2% (n=5) male, were included in the study. Papillary microcarcinoma was the pathological diagnosis in 24.2% (n=15) of the cases. EBV was identified in 58.06% (n=36) of the tumor cells nuclei, 58.06% (n=36) in the tumor cell cytoplasm, 16.12% (n=10) in tumor infiltrative lymphocytes, and 53.2% (n=33) in normal parenchymal follicle epithelial cells (NPFEC). In the T2 stage, the rate of EBV nuclear positivity in patients was significantly higher (p=0.034). The classic variant of papillary carcinoma was accompanied by a significantly higher rate of EBV-negative NPFEC (67.6%, p=0.049). In multifocal tumors, EBV positivity was found to be significantly higher in lymphocytes in the surrounding tissues (58.3%, p=0.034). Conclusion A significant increase in EBV positivity in the surrounding tissue lymphocytes was observed in multifocal PTC developing on a background of HT. This suggests a possible association between HT and EBV. [ABSTRACT FROM AUTHOR]

Abstract Objectives While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. Methods This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. Results There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P

Abstract Background Papillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto’s thyroiditis, presenting significant challenges in clinical diagnosis and treatment. Case demonstration A 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis. Conclusions The concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto’s thyroiditis. The patient’s favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases.

Aims:Approximately 80-85% of thyroid malignancies are papillary thyroid cancer (PTC). This study evaluated the relationship between thyroid capsule invasion (TCI) in PTC and macroscopic histopathological findings.Methods:A single-center, retrospective study was conducted using the medical records of adult patients who underwent PTC surgery. The patients were classified as TCI (+) or TCI (-) based on the postoperative pathological examination. Tumor localization, calcification, and multifocality were evaluated between the two groups.Results:The study included 236 patients (mean age: 44.3±12.0 years, female sex: 76.7%). Preoperative basic characteristics, comorbidities, thyroid function status, nodule calcification, halo border irregularity, and nodule diameter on ultrasonography were similar between the two groups. However, more TCI (+) patients had positive or suspicious fine needle aspiration biopsy findings preoperatively. The duration of surgery was longer in TCI (+) patients (86 minutes vs. 75 minutes, p1 mm was more common in TCI (+) vs. TCI (-) patients (47.3% vs. 81.8%, p

Background: Papillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto's thyroiditis, presenting significant challenges in clinical diagnosis and treatment. Case demonstration: A 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis. Conclusions: The concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto's thyroiditis. The patient's favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of metastatic thyroid carcinoma to the pancreas, which presented as a poorly differentiated carcinoma and mimicked pancreatic ductal adenocarcinoma (PDA) in terms of morphology. The patient, a 71-year-old man with a history of papillary thyroid carcinoma (PTC), underwent endoscopic ultrasound fine-needle aspiration (EUS-FNA) to confirm the presence of a pancreatic mass. The aspirate smears showed atypical cells with features of poorly differentiated carcinoma, but immunohistochemical studies confirmed the thyroid origin of the tumor. Molecular analysis revealed a novel AGAP3::BRAF gene fusion. This case highlights the importance of considering metastatic thyroid carcinoma in the differential diagnosis of pancreatic masses and the potential for unique molecular findings in these cases. [Extracted from the article]

In clinical practice, contralateral incidental malignant foci (CIMFs) can be found in some early (cT1N0M0) papillary thyroid carcinomas (PTCs) on postoperative pathological examination. To screen out the patients with high risk of CIMF preoperatively would help in determining the extent of thyroid surgery. From October 2016 to February 2021, 332 patients diagnosed with early (cT1N0M0) PTC who underwent total thyroidectomy were included and randomly allocated into a training dataset (n = 233) and a test dataset (n = 99). Demographic and clinicopathological features were recorded and analyzed using logistic regression analysis. A coefficient-based nomogram was developed and validated. Logistic regression analyses revealed that the predictive model including BRAF V600E mutation, multifocality and margin of the contralateral nodule achieved the best diagnostic performance. The nomogram showed good discrimination, with AUCs of 0.795 (95 % CI, 0.736–0.853) for the training set and 0.726 (95 % CI, 0.609–0.843) for the test set. The calibration curve of the nomogram presented good agreement. The risk stratification system can be used to quantify the probability of CIMF and may assist in helping the patients choose total thyroidectomy or thyroid lobectomy with early (cT1N0M0) PTC. • Contralateral incidental malignant foci (CIMFs) can be found in some early PTCs. • BRAF V600E mutation, multifocality and contralateral nodule margin predict CIMFs. • The nomogram would help in screening those patients with high risk of CIMFs. • The nomogram may help in determining the extent of thyroid surgery preoperatively. [ABSTRACT FROM AUTHOR]

Aims: Approximately 80-85% of thyroid malignancies are papillary thyroid cancer (PTC). This study evaluated the relationship between thyroid capsule invasion (TCI) in PTC and macroscopic histopathological findings. Methods: A single-center, retrospective study was conducted using the medical records of adult patients who underwent PTC surgery. The patients were classified as TCI (+) or TCI (-) based on the postoperative pathological examination. Tumor localization, calcification, and multifocality were evaluated between the two groups. Results: The study included 236 patients (mean age: 44.3±12.0 years, female sex: 76.7%). Preoperative basic characteristics, comorbidities, thyroid function status, nodule calcification, halo border irregularity, and nodule diameter on ultrasonography were similar between the two groups. However, more TCI (+) patients had positive or suspicious fine needle aspiration biopsy findings preoperatively. The duration of surgery was longer in TCI (+) patients (86 minutes vs. 75 minutes, p<0.001), whereas the length of hospital stay was similar. Surgical margin >1 mm was more common in TCI (+) vs. TCI (-) patients (47.3% vs. 81.8%, p<0.001). Postoperative macroscopic pathological reports showed that middle lobe tumor localization was more common in TCI (+) (38.2%) than in TCI (-) (23.2%) patients (p=0.028), whereas tumor localization in the upper pole, lower pole, and isthmus was not different. Multifocal involvement (41.8% vs. 38.1%) was also similar between the two groups. Conclusions: This study showed that fine needle biopsy positivity and nodule localization in the middle thyroid gland were more common in TCI (+) PTC patients as detected postoperatively. The other macroscopic pathological findings were not different. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether ultrasound-guided radiofrequency ablation (RFA) is reliable for unifocal T1aN0M0 papillary thyroid carcinoma in the isthmus (PTCI). Methods: 431 patients who underwent ultrasound-guided RFA for unifocal T1aN0M0 papillary thyroid carcinoma (PTC) were divided by location of the lesion into the PTCI group (52 females, 7 males, mean age 43.79 ± 12.04 years, range 22-74 years) and the PTCL group ((291 females, 81 males, mean age 43.42 ± 10.87 years, range 18-75 years) for comparative analysis. The efficacy of ultrasound-guided RFA was evaluated by volume reduction rate (VRR), complete disappearance rate (CDR) and disease progression, and the safety was evaluated by incidence of complications. Results: The two groups exhibited a consistent trend of change, with the PTCI group performing better in volume, VRR and CDR at all follow-up time points expect 1 month, but the differences were not statistically significant (p > 0.05). The mean initial volume of the PTCI group vs the PTCL group decreased significantly from 65.4 ± 69.79 vs 86.38 ± 87.09 mm³ (range 10.92-427.58 vs 3.05-471.6 mm³) to 0 vs 0 mm³ at a mean follow-up time of 31.12 ± 12.5 months (range 12-60 months); their VRR increased significantly from −618.62 ± 655.61% vs −789.85 ± 1135.07% at 1 month to 100% vs 100% at 48 months. No disease progression was found in the two groups. The PTCI group had no complications, whereas the PTCL group had a total of 7 complications (1.88%). Conclusions: Ultrasound-guided RFA is reliable for unifocal T1aN0M0 PTCI. It can be promoted as an alternative to immediate surgery for selected PTC patients. [ABSTRACT FROM AUTHOR]

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA). Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays.Results:eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis. Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells.

Background: Hashimoto's thyroiditis (HT) is an independent risk factor for papillary thyroid carcinoma (PTC), but the underlying mechanism remains unknown. The incidence of PTC in patients with HT is significantly elevated, and the presence of both HT and PTC contributes to a higher rate of misdiagnosis. Materials and Methods: Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the thyroid nodule gene chip dataset from GEO Datasets. Serum and clinical data from 191 patients with thyroid nodules at the affiliated hospital were collected for analysis. Experimental techniques, including real-time quantitative PCR, ELISA, immunohistochemistry (IHC), and enzyme activity detection, were used to measure the level of dipeptidyl peptidase 4 (DPP4) in thyroid nodule tissues and serum. Results: Thyroid nodules in patients with HT and PTC exhibit high levels of DPP4, along with elevated concentrations of soluble DPP4 in the serum. These findings demonstrate the potential predictive value of soluble DPP4 for PTC diagnosis. Conclusions: The concentration and enzymatic activity of soluble DPP4 in serum can serve as diagnostic biomarkers for patients with HT-associated PTC. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of overexpression of miR3753p on the proliferation and invasion of thyroid papillary carcinoma cells, and to clarify the mechanism. Methods The miR3753p expression in the human thyroid epithelial cell line Nthyori31 and human thyroid papillary carcinoma cell lines TPC1, BHP516, BHP27, and K1 was detected by RTqPCR. Thyroid papillary carcinoma cell line TPC1 which had the lowest expression of miR375 3p was taken and divided into the transfected group and negative control group. In the transfected group, we upregulated the expression of miR3753p in thyroid cancer cell line TPC1 by transfecting miR3753p mimics, while cells in the the negative control group were transfected with negative control sequences （scramble）. The cell proliferation capacities of two groups were observed by MTT assay. Invasion capacities were observed by Transwell assay. The expression levels of PI3K/ AKT signaling pathwayrelated proteins pPI3K and pAKT and epithelialmesenchymal transition （EMT）related proteins Ecadherin, Ncadherin, and Vimentin were detected by Western blotting. PTC cells were randomly divided into the nega tive control group, miR3753p overexpression group, and miR3753p overexpression+IGF1 group. Cells in the miR3753p overexpression group and negative control group were transfected with miR3753p mimics （miR3753p mimics） and negative control sequence （scramble） through LifefectamineTM3000, respectively. Cells in the miR3753p overex pression+IGF-1 group were treated with miR-375-3p mimics and the PI3K/AKT signal pathway agonist insulin-like growth factor-1（IGF-1). The proliferative and invasive capacities of cells in the three groups were observed. Results The ex pression levels of miR-375-3p in cell lines TPC-1, BHP5-16, BHP2-7 and K-1 were significantly lower than that of normal human thyroid epithelial cell line Nthy-ori3-1（all P<0. 05). The OD values of the miR-375-3p over-expression group were significantly lower than those of the negative control group at 24，48 and 72 h after transfection （all P<0. 05）, and the number of invasive cells was smaller （P<0. 05). Compared with the negative control group, the expression levels of pPI3K and p-AKT in the miR-375-3p over-expression group decreased, the expression levels of E-cadherin increased, and the expression levels of N-cadherin and Vimentin decreased （all P<0. 05). After adding IGF-1, compared with the miR375-3p over-expression group, the proliferative OD value and the number of invasion cells in the miR-375-3p over-expres sion+IGF-1 group increased （all P<0. 05). Conclusion MiR-375-3p is down-regulated in thyroid carcinoma cell lines； over-expression of miR-375-3p can inhibit cell proliferation and invasion, and the mechanism may be related to the inhibi tion of PI3K/AKT/EMT signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Reduced field‐of‐view diffusion‐weighted imaging (rFOV‐DWI) could be proved to quantitatively identify papillary thyroid carcinoma (PTC) and there is no literature regarding the use of T1 mapping to distinguish nodular goiter (NG) from PTC. Purpose: To compare T1 mapping with rFOV‐DWI in differentiating NG and PTC. Study Type: Prospective study. Populations: Ninety‐five hospitalized patients with thyroid nodules were included in the research. Sequence: All subjects underwent T1‐weighted imaging, T2‐weighted imaging, rFOV‐DWI and T1‐mapping sequences. Assessment: The apparent diffusion coefficient (ADC) and T1 values of each thyroid nodule were measured, respectively. According to pathological results, the thyroid nodules were divided into two groups: Group 1 (NG) and Group 2 (PTC). Statistical Tests: An independent sample t test was used to evaluate the differences of ADC and T1 between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of T1, ADC, Thyroid Imaging Reporting and Data System (TI‐RADS) and T1 and ADC. Results: The T1 and ADC values of nodular goiter were both higher than those of PTC (p < 0.05). The area under the ROC curve (AUC) values of T1 and ADC were significantly higher than that of T1 or ADC alone (p < 0.05). The AUC value of T1 and ADC was as same as that of TI‐RADS. Conclusion: The combination of T1 mapping and rFOV‐DWI could effectively differentiate NG from PTC. And it has at least the same diagnostic value as the ultrasound‐based TI‐RADS classification. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to explore diagnostic performance based on clinical characteristics, conventional ultrasound, Angio PLUS (AP), shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) for the preoperative evaluation of cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) and to find a reliable predictive model for evaluating CLNM.Materials and methodsA total of 206 thyroid nodules in 206 patients were included. AP, SWE, and CEUS were performed for all thyroid nodules. Univariate analysis and multivariate logistic regression analysis were performed to ascertain the independent risk factors. The sensitivity, specificity, and the area under the curve (AUC) of independent risk factors and the diagnostic model were compared.ResultsSex, age, nodule size, multifocality, contact extent with adjacent thyroid capsule, Emax, and capsule integrity at CEUS were independent risk predictors for CLNM in patients with PTC. A predictive model was established based on the following multivariate logistic regression: Logit (p) = −2.382 + 1.452 × Sex − 1.064 × Age + 1.338 × Size + 1.663 × multifocality + 1.606 × contact extent with adjacent thyroid capsule + 1.717 × Emax + 1.409 × capsule integrity at CEUS. The AUC of the predictive model was 0.887 (95% CI: 0.841–0.933), which was significantly higher than using independent risk predictors alone.ConclusionOur study found that male presence, age < 45 years, size ≥ 10 mm, multifocality, contact extent with adjacent thyroid capsule > 25%, Emax ≥ 48.4, and interrupted capsule at CEUS were independent risk predictors for CLNM in patients with PTC. We developed a diagnostic model for predicting CLNM, which could be a potentially useful and accurate method for clinicians; it might be beneficial to surgical decision-making and patient management and for improving prognosis.

Objective To predict the probability of occult lymph node metastasis (OLM) in the central region of the neck by analyzing the dual-energy CT energy spectrum curve of thyroid papillary carcinoma (PTC）. Methods Patients with PTC confirmed by pathology before and after operation were retrospectively collected. CT images were analyzed by radiologists. There were 140 cases without cervical lymph node metastasis. Among them， 88 patients with occult lymph node metastasis in the central group (OLM+) and 52 patients without metastasis (OLM−) were confirmed by pathology. The CT value of PTC on each single energy image was measured and the slope (k) of the energy spectrum curve was calculated. The differences in parameters between the two groups were analyzed. Results (1) the karterial，40 keVarterial，40 keVvenous，160 keVvenous and 180 keVvenous of PTC between OLM+ group and OLM− group in arterial and venous phase were significantly different (P < 0.05) . (2) The AUC of 40 keVarterial，karterial，40 keVvenous，160 keVvenous and 180 keVvenous in PTC were 0.590，0.622，0.590，0.429 and 0.424 respectively. When karterial = 2.563，the sensitivity and accuracy of diagnosing PTC with OLM in the central group were 93.2% and 69.3%. When 40 keVvenous = 370.25，the specificity of PTC with OLM was 86.5%. Conclusion The energy spectrum curve of PTC has a certain reference value in predicting occult lymph node metastasis in the central region of the neck. karterial has the highest sensitivity and 40 keVvenous has the highest specificity. [ABSTRACT FROM AUTHOR]

A 65‐year‐old man with a history of Hashimoto's thyroiditi on Levothyroxine developed Graves' disease with ocular symptoms and was treated with teprotumumab without improvement. Total thyroidectomy was performed to control hyperthyroidism. Surgical pathology revealed multifocal papillary thyroid carcinoma. Rarely, a spectrum of thyroid disorders is seen in a single patient. [ABSTRACT FROM AUTHOR]

Abstract Background Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. Methods The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. Results We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. Conclusions Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.

Background and purpose: Multinodular goiter is a benign enlargement of thyroid gland and papillary thyroid carcinoma is the most common type of thyroid cancer. Today, immunohistochemical markers can be used in diagnosis and prognosis of tumors. The aim of this study was to compare the expression of CD117 in multinodular goiter and papillary thyroid carcinoma and its association with prognostic factors. Materials and methods: In this cross-sectional study, samples of thyroid tissue from 60 multinodular goiter and 60 papillary thyroid carcinoma cases who underwent thyroidectomy in Tehran Mostafa Khomeini Hospital during 2011-18, were evaluated for CD117 expression via immunohistochemistry. The expression intensity was scored 0-3. Results: CD117 was expressed in all samples with generally lower expression scores in malignant samples: 95% and 5% of malignant cases showed scores 1 and 2, respectively. Almost 52% and 48% of benign cases showed score 1 and scores 2 and 3, respectively (P

Abstract Background Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. Methods The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. Results The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. Conclusion BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

Thyroglossal duct papillary carcinoma is extremely rare in clinical practice.This article reports a case of a thyroglossal duct cyst complicated by thyroid papillary carcinoma,while also reviewing the relevant literature.It summarizes the clinical manifestations,imaging characteristics,and pathological features of thyroglossal duct papillary carcinoma and discusses the relationship between thyroglossal duct cysts,malignant transformation of thyroglossal duct cysts,and thyroid papillary carcinoma.

Background/aim: This study compared the initial outcomes of gas-insufflation one-step single-port transaxillary (GOSTA) robotic thyroidectomy with traditional open thyroidectomy for thyroid cancer at a single institution., Patients and Methods: A retrospective analysis was conducted on 77 patients who underwent thyroidectomy for differentiated thyroid cancer from January to June 2024. Exclusion criteria included benign nodules, Graves' disease, and previous thyroid surgeries. Two surgeons performed the procedures, with one having no prior robotic surgery experience., Results: Of the 77 patients, 48 underwent open thyroidectomy and 29 underwent GOSTA thyroidectomy. The GOSTA group had a significantly lower mean age (40.1 vs. 47.6 years, p=0.002) and a higher proportion of female patients (p=0.040). The open group patients had more harvested lymph nodes than the GOSTA group patients (7.9 vs. 2.4, p<0.001). The GOSTA group patients had longer operation time (156.4 vs. 80.6 min, p<0.001), and had extended hospital stay than the open group patients (5.9 vs. 3.4 days, p<0.001). Complication rates were similar between the groups., Conclusion: GOSTA robotic thyroidectomy provides comparable safety and effectiveness to open thyroidectomy, with improved cosmetic outcomes despite longer operation times and hospital stays. This technique is feasible for surgeons without prior robotic experience, offering a viable alternative for patients prioritizing cosmetic results., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid, and its invasiveness and metastatic ability are closely related to patient prognosis. Chaperonin containing TCP1 subunit 2 (CCT2) is an important component of the molecular chaperone protein complex and has been shown to regulate cell proliferation and migration in various tumors. Epithelial-mesenchymal transition (EMT) is a critical process in tumor metastasis, and Zinc Finger E-Box Binding Homeobox 1 ( ZEB1 ) is a core transcription factor that regulates EMT. This study aims to explore how CCT2 induces EMT gene transcription through ZEB1 , thereby promoting the metastasis and tumorigenesis of PTC., Methods: CCT2 in PTC tissues was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. siRNA and overexpression vectors were used to silence and overexpress CCT2 , respectively, and the effects on PTC cell migration, invasion, proliferation, and apoptosis were observed. Rescue experiments were used to investigate the effect of CCT2 on ZEB1 and EMT-related genes. Cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay. Silencing ZEB1 was used to verify its effect on the oncogenic activity of CCT2 ., Results: CCT2 was found to be highly expressed in PTC tissues ( p < 0.01). In in vitro and in vivo experiments, silencing CCT2 inhibited the migration and invasion of PTC cells and their metastasis, while overexpression of CCT2 produced the opposite effect. Additionally, CCT2 promoted PTC cell proliferation and inhibited apoptosis ( p < 0.01). Mechanistic studies revealed that CCT2 upregulated ZEB1 expression ( p < 0.01), thereby inducing EMT gene transcription ( p < 0.01). Silencing ZEB1 reduced the oncogenic effect of CCT2 ., Conclusion: This study first revealed the high expression of CCT2 in PTC and its essential role in the migration, invasion, proliferation, and anti-apoptosis of tumor cells. CCT2 promotes the metastasis and tumorigenesis of PTC by regulating ZEB1 and EMT-related genes. These findings provide new potential targets for molecular targeted therapy of PTC and explore new directions for future clinical treatment strategies.

Background: High-volume lymph node metastasis (HVLNM, equal to or more than 5 lymph nodes) is one of the adverse features indicating high recurrence risk in papillary thyroid carcinoma (PTC) and is recommended as one of the indications of completion thyroidectomy for patients undergoing thyroid lobectomy at first. In this study, we aim to develop a preoperative nomogram for the prediction of HVLNMs in the central compartment in PTC (cT1-2N0M0), where preoperative imaging techniques perform poor. Methods: From October 2016 to April 2021, 423 patients were included, who were diagnosed as PTC (cT1-2N0M0) and underwent total thyroidectomy and prophylactic central compartment neck dissection in our center. Demographic and clinicopathological features were recorded and analyzed using univariate and multivariate logistic regression analysis. A nomogram was developed based on multivariate logistic regression analysis. Results: Among the included patients, 13.4% (57 cases) were found to have HVLNMs in the central compartment. Univariate and multivariate logistic regression analysis showed that age (35 years), BRAF with V600E mutated, nodule diameter, and calcification independently predicted HVLNMs in the central compartment. The nomogram showed good discrimination with an AUC of 0.821 (95% CI, 0.768–0.875). Conclusion: The preoperative nomogram can be used to quantify the probability of HVLNMs in the central compartment and may reduce the reoperation rate after thyroid lobectomy. [ABSTRACT FROM AUTHOR]

BackgroundHigh-volume lymph node metastasis (HVLNM, equal to or more than 5 lymph nodes) is one of the adverse features indicating high recurrence risk in papillary thyroid carcinoma (PTC) and is recommended as one of the indications of completion thyroidectomy for patients undergoing thyroid lobectomy at first. In this study, we aim to develop a preoperative nomogram for the prediction of HVLNMs in the central compartment in PTC (cT1-2N0M0), where preoperative imaging techniques perform poor.MethodsFrom October 2016 to April 2021, 423 patients were included, who were diagnosed as PTC (cT1-2N0M0) and underwent total thyroidectomy and prophylactic central compartment neck dissection in our center. Demographic and clinicopathological features were recorded and analyzed using univariate and multivariate logistic regression analysis. A nomogram was developed based on multivariate logistic regression analysis.ResultsAmong the included patients, 13.4% (57 cases) were found to have HVLNMs in the central compartment. Univariate and multivariate logistic regression analysis showed that age (35 years), BRAF with V600E mutated, nodule diameter, and calcification independently predicted HVLNMs in the central compartment. The nomogram showed good discrimination with an AUC of 0.821 (95% CI, 0.768–0.875).ConclusionThe preoperative nomogram can be used to quantify the probability of HVLNMs in the central compartment and may reduce the reoperation rate after thyroid lobectomy.

Background: Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. It has an excellent prognosis, with a 10-year survival rate of more than 95 per cent, although outcome is poorer for aggressive subtypes. Aim of the Work: Our work in this study shows that the incidence of recurrence post hemi thyroidectomy is significantly higher compared to post total thyroidectomy and in case of multifocal and insular carcinoma with hemi thyroidectomy it increases the incidence of recurrence and drastically affecting the 10-year survival rate and the quality of life. Material and Methods: We followed the PRISMA statement guideline during this systematic review and meta-analysis preparation and performed all steps according to the Cochrane handbook of systematic reviews of intervention. We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and Science Direct till November 2021 relevant keywords. We used the following search strategy for searching different databases: ("Papillary Thyroid Cancer" OR "Papillary Thyroid Cancers" OR "Papillary Thyroid Carcinomas" OR "Papillary Carcinoma Of Thyroid" OR "Papillary Thyroid Carcinoma" OR "Familial Non medullary Thyroid Cancer" OR "Non medullary Thyroid Carcinoma" OR "Non medullary Thyroid Carcinomas" OR "Thyroid Carcinoma, Non medullary" OR "Thyroid Carcinomas, Non medullary") AND (Hemithyroidectomy OR Thyroidectomy OR Thyroidectomies OR thyroid removal). All the references of the included studies were searched for relevant studies. Results: Multifocality and insular carcinoma and bilaterality increase the incidence of recurrence drastically so it is recommended for total thyroidectomy. Gender plays a role in the aggressiveness of the tumor but not in the incidence of recurrence as this is determined by the selection criteria of the candidate and the surgical technique. We studied 7 risk factors through this meta-analysis and it is recommended for application of LNR as a post op prognostic tool for recurrence and to apply hemi thyroidectomy for tumor size <2 cm instead of < 4 also meticulous pre-operative workup, accurate risk assessment, stratification and staging this is to customize a road map for every patient through a multi-disciplinary team. Conclusion: In this meta-analysis we found that in low grade differentiated papillary thyroid carcinoma the recurrence is higher with hemithyroidectomy than in total thyroidectomy after applying the ATA guidelines for 10 years retrospectively but in case of 10 year survival it showed no significant difference. [ABSTRACT FROM AUTHOR]

Marine-Lenhart syndrome is a name given to the coexistence of Graves' disease and functional nodules. In this rare syndrome, nodules are mostly benign. The most common extrathyroidal manifestation of Graves' disease is Graves' orbitopathy. It is usually seen bilaterally but can also be seen unilaterally. In this article, a case with Marine-Lenhart syndrome, metastatic thyroid papillary carcinoma, and unilateral Graves' orbitopathy is presented. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common endocrine malignancy that its incidence hascontinuously increased in recent decades all over the world. Thyroid cancer in Iranis the seventh most common cancer in women and the 14th in men and the 11th mostcommon cancer in both genders. The study on the methylation status of RASSF1Agene promoter has shown that this gene is methylated in 35% of benign andmalignant thyroid tumors. Hypermethylation of the RASSF1A gene use for thedifferentiation of benign tumors from malignant of thyroid gland. The aim of thisstudy was to determine the sensitivity and specificity of DNA methylation ofRASSF1A gene in the differential diagnosis of benign tumors from papillary thyroidcarcinoma.160 samples of patients with malignant thyroid tumors (80 samples) andbenign thyroid (80 samples) were entered into this study from all patients referringto Ahwaz medical centers. The Hypermethylation of the gene after DNA extractionwas done by COBRA method. Finally, for calculating sensitivity and specificity ofthe two tests were done by epidemiological calculations.The sensitivity andspecificity of Hypermethylation of the RASSF1A gene test were 91.25% and 15%respectively.Hypermethylation of the promoter of the RASSF1A gene as a diagnosistest is more sensitive to differential diagnosis of benign tumors from papillarythyroid carcinoma.

Objective To explore the feasibility of totally endoscopic thyroidectomy (TET) for thyroid papillary carcinoma in cT1N0 stage. Methods Clinical data of 287 patients with primary cT1N0 thyroid papillary cancer underwent thyroidectomy in our hospital from March 2016 to June 2018 were collected and retrospectively analyzed, including 145 patients undergoing TET (TET group) and 142 patients by open thyroidectomy (OT group). The intraoperative conditions, complications, recurrence and cosmetic effect were compared between the 2 groups. Results There were no significant differences in the general data of the patients in the TET group and OT group, including mean age (P=0.283), sex ratio (P=0.344), tumor size (P=0.265) and tumor distribution (P=0.872). In terms of surgical effects, no significant differences were observed in the numbers of central neck lymph node dissections (CNLN) (P=0.847) and metastatic lymph nodes (P=0.839) between the 2 groups for the patients with lateral lobectomy and lateral central neck dissection. The TET group had significantly smaller volume of intraoperative bleeding (P < 0.001), and longer operation time (P < 0.001) when compared with the OT group. For those with bilateral lobectomy and lateral central neck dissection, there were no significant differences in the numbers of central neck lymph node dissections (P=0.092) and metastatic lymph nodes (P=0.241) between the 2 groups. The amount of intraoperative bleeding was smaller (P < 0.001) and the operation time were longer in the TET group (P < 0.001) than the OT group. For surgical complications, there were no significant differences in the incidences of temporary/permanent hyperparathyroidism and recurrent laryngeal nerve injury between the 2 group (P>0.05). No hemorrhagic subcutaneous fluid or wound infection occurred in the TET group. The TET group had significantly better cosmetic effect than the OT group (P < 0.001). The patients were followed up for 6 to 30 months, and no recurrence was observed. Conclusion TET treatment is safe and feasible for cT1N0 thyroid papillary cancer. TET treatment might be an optional approach for the patients with cosmetic demand.

Jun Zhang,1–4 Linfei Hu,2–5 Huijuan Wang,2–5 Jingtai Zhi,2–5 Xiukun Hou,2–5 Yu Wu,6 Xiangqian Zheng,2–5 Ming Gao2–51Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 4Department of Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 5Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 6Department of Head and Neck Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, People’s Republic of ChinaObjective: Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) is a major producer of mitochondrial NADPH. IDH2-related research has focused on its mutation mechanism and its clinical significance, but the role of wild-type IDH2 in carcinoma remains controversial. Altered IDH2 levels have been identified in several types of carcinomas. However, the significance and expression of IDH2 in thyroid cancer remains unknown.Methods: We examined the expression of IDH2 in thyroid cancer and adjacent normal tissues using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining analyses, and western blot analysis with frozen tissues. The relationship between IDH2 and the clinicopathological features of thyroid cancer was analyzed by IHC. Subsequently, we investigated the function of wild-type IDH2 in thyroid cancer cells in vitro.Results: We found that the mRNA expression and protein levels of IDH2 were higher in tumor than in adjacent tissues, when evaluated by qRT-PCR, western blot, and IHC analyses. Tumor size, T stage, lymph node metastasis, and TNM stage showed significant differences between the IDH2 high expression and low expression groups. Multiple logistic regression analyses indicated that tumor size and IDH2 expression were significantly correlated with the occurrence of neck LNM. Furthermore, CCK8 levels, colony formation, and invasive cell number were decreased in the sh-IDH2 groups. The upregulation of IDH2 in thyroid cancer cells showed opposite effects.Conclusion: Our results indicated that IDH2 may play an important role in the development of thyroid cancer. IDH2 can be used as a potential biomarker for diagnosis and prognosis and may be a potential therapeutic target for thyroid cancer.Keywords: thyroid papillary carcinoma, IDH2, function analysis, therapeutic target

Objective To investigate the effect of inhibiting FoxM1 gene expression on glucose uptake and lactic acid production in papillary thyroid carcinoma (PTC) cells, and to explore the correlation between FoxM1 and PTC cell glycolysis pathway. Methods The expression of FoxM1 mRNA and protein in PTC TPC-1 cells were detected after lentiviral rLv-hFoxM1 transfection. The effect of inhibiting FoxM1 gene expression on TPC-1 cell viability was detected by MTT method. The changes of glucose intake and lactic acid production in TPC-1 cells transfected with lentiviral rLv-hFoxM1 and the content of the key enzymes of hexokinase isoform 1 (HK1), hexokinase isoform 2 (HK2) and glucose transporter 1 (Glut1) were detected by Western blot. Results In TPC-1 cells, lentiviral rLv-hFoxM1 transfection significantly inhibited the expression of FoxM1 mRNA and protein in TPC-1 cells and the activity of TPC-1 cells was significantly decreased (P < 0.05). After the FoxM1 gene was inhibited, the glucose intake and the lactic acid production of TPC-1 cells were significantly decreased (P < 0.01). The levels of Glut1, HK1 and HK2 were also significantly decreased (P < 0.01). Conclusion Inhibition of FoxM1 gene expression could reduce the level of glycolysis in PTC cells.

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. Methods: The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. Results: We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. Conclusions: Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common endocrine malignancy, and thyroid carcinoma (PTC) has the highest incidence rate, accounts for about 85%~90% of thyroid carcinoma. There are many markers of PTC, such as murine sarcoma viral oncogene homolog B1 (BRAF), telomerase reverse transcriptase, Ki-67, microRNA-146b, PDZ and LIM domain 5 (PDLIM5). Among them, BRAF plays an important role in the carcinogenesis, development and prognosis of PTC. This article summarizes the research progress of BRAF signaling pathway, its role in the carcinogenesis, development and prognosis of PTC, its clinical correlation with the clinical pathological characteristics of PTC, and its application in the diagnosis and treatment of PTC to provide the references to readers. [ABSTRACT FROM AUTHOR]

Objective: To analyze the radiomic and clinical features extracted from 2D ultrasound images of thyroid tumors in patients with Hashimoto's thyroiditis (HT) combined with papillary thyroid carcinoma (PTC) using machine learning (ML) models, and to explore the diagnostic performance of the method in making preoperative noninvasive identification of cervical lymph node metastasis (LNM)., Methods: A total of 528 patients with HT combined with PTC were enrolled and divided into two groups based on their pathological results of the presence or absence of LNM. The groups were subsequently designated the With LNM Group and the Without LNM Group. Three ultrasound doctors independently delineated the regions of interest and extracted radiomic features. Two modes, radiomic features and radiomics-clinical features, were used to construct random forest (RF), support vector machine (SVM), LightGBM, K-nearest neighbor (KNN), and XGBoost models. The performance of these five ML models in the two modes was evaluated by the receiver operating characteristic (ROC) curves on the test dataset, and SHapley Additive exPlanations (SHAP) was used for model visualization., Results: All five ML models showed good performance, with area under the ROC curve (AUC) ranging from 0.798 to 0.921. LightGBM and XGBoost demonstrated the best performance, outperforming the other models ( P <0.05). The ML models constructed with radiomics-clinical features performed better than those constructed using only radiomic features ( P <0.05). The SHAP visualization of the best-performing models indicated that the anteroposterior diameter, superoinferior diameter, original&#95;shape&#95;VoxelVolume, age, wavelet-LHL&#95;firstorder&#95;10Percentile, and left-to-right diameter had the most significant effect on the LightGBM model. On the other hand, the superoinferior diameter, anteroposterior diameter, left-to-right diameter, original&#95;shape&#95;VoxelVolume, original&#95;firstorder&#95;InterquartileRange, and age had the most significant effect on the XGBoost model., Conclusion: ML models based on radiomics and clinical features can accurately evaluate the cervical lymph node status in patients with HT combined with PTC. Among the 5 ML models, LightGBM and XGBoost demonstrate the best evaluation performance., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

This study examined metabolite profile differences between serum samples of thyroid papillary carcinoma (PTC) patients and healthy controls, aiming to identify candidate biomarkers and pathogenesis pathways in this cancer type. Serum samples were collected from PTC patients (n = 80) and healthy controls (n = 80). Using principal component analysis (PCA), partial least squares discrimination analysis(PLS-DA), orthogonal partial least square discriminant analysis (OPLS-DA), t-tests, and the volcano plot, a model of abnormal metabolic pathways in PTC was constructed. PCA, PLS-DA, and OPLS-DA analysis revealed differences in serum metabolic profiles between the PTC and control group. OPLS-Loading plot analysis, combined with Variable importance in the projection (VIP)>1, Fold change (FC) > 1.5, and p < 0.05 were used to screen 64 candidate metabolites. Among them, 22 metabolites, including proline betaine, taurocholic acid, L-phenylalanine, retinyl beta-glucuronide, alpha-tocotrienol, and threonine acid were upregulated in the PTC group; meanwhile, L-tyrosine, L-tryptophan, 2-arachidonylglycerol, citric acid, and other 42 metabolites were downregulated in this group. There were eight abnormal metabolic pathways related to the differential metabolites, which may be involved in the pathophysiology of PTC. Six metabolites yielded an area under the receiver operating curve of >0.75, specifically, 3-hydroxy-cis-5-tetradecenoylcarnitine, aspartylphenylalanine, l-kynurenine, methylmalonic acid, phenylalanylphenylalanine, and l-glutamic acid. The Warburg effect was observed in PTC. The levels of 3-hydroxy-cis-5-tetradecenoylcarnitine, aspartylphenylalanine, l-kynurenine, methylmalonic acid, phenylalanine, and L-glutamic acid may help distinguish PTC patients from healthy controls. Aspartic acid metabolism, glutamic acid metabolism, urea cycle, and tricarboxylic acid cycle are involved in the mechanism of PTC.

Background and purpose: Multinodular goiteris a benign enlargement of thyroid gland and papillary thyroid carcinoma is the most common type of thyroid cancer. Today, immunohistochemical markers can be used in diagnosis and prognosis of tumors. The aim of this study was to compare the expression of CD117 in multinodular goiter and papillary thyroid carcinoma and its association with prognostic factors.Materials and methods:In this cross-sectional study, samples of thyroid tissue from 60 multinodular goiter and 60 papillary thyroid carcinoma cases who underwent thyroidectomy in Tehran Mostafa Khomeini Hospital during 2011-18, were evaluated for CD117 expression via immunohistochemistry. The expression intensity was scored 0-3.Results:CD117 was expressed in all samples with generally lower expression scores in malignant samples: 95% and 5% of malignant cases showed scores 1 and 2, respectively. Almost 52% and 48% of benign cases showed score 1 and scores 2 and 3, respectively (P<0.05). Increased CD117 expression was associated with decreased lymph node involvement and increased tumor size (P<0.05), but there was no significant relationship between this marker and other prognostic variables (P=0.081). Conclusion:There are contradictory findings on the relation between CD117 expression and prognostic factors in malignant cases, therefore, further studies are recommended to clarify the association. [ABSTRACT FROM AUTHOR]

• Thyroglossal duct cyst carcinoma concurrent with another thyroid gland carcinoma as two separate tumours are rare. • Ultrasound scan and ultrasound-guided fine needle aspiration and cytology are useful for diagnosis and for follow up. • Excision of thyroglossal duct cyst carcinoma and total thyroidectomy is ideal treatment option to facilitate future radioactive iodine ablation if required. Malignancy of thyroglossal duct cyst (TGDC) is rare, usually as papillary carcinoma, and less frequently as squamous cell or follicular carcinoma. TGDC carcinoma can present as a mass arising from the neck, with or without compression symptoms. Papillary carcinoma in TGDC concomitant with another papillary carcinoma in the thyroid gland is extremely rare. : 31 years old female with a neck lump since 2 years, slowly increasing in size, with mild pain while drinking fluids, and no change of voice. No past history of neck irradiation or family history of thyroid cancers. Ultrasonography of the neck showed TGDC and right thyroid nodule. Ultrasound guided fine needle aspiration and cytology of the TGDC showed TGDC papillary carcinoma. The patient underwent Sistrunk's procedure and total thyroidectomy. Rare case of classic papillary carcinoma arising in TGDC, concomitant with another papillary carcinoma in the right thyroid nodule. Preoperative work up included US and fine needle aspiration and cytology (FNAC). Post-operative histopathology showed papillary carcinoma in the TGDC; and another in the right thyroid lobe that was a papillary carcinoma with follicular patterns. TGDC carcinoma concurrent with another carcinoma in the right thyroid lobe as two separate tumours are extremely rare. All patients should undergo Sistrunk's procedure, and total thyroidectomy for the thyroid tumour. Follow-up requires thyroxine replacement therapy to treat hypothyroidism and to suppress TSH in order to prevent recurrence; and neck ultrasound and thyroglobulin tumour marker to detect recurrence if present. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical value of ultrasonography in diagnosis of cervical lymph node metastasis of thyroid papillary carcinoma (PTC), and to analyze the correlation between blood flow parameters and lymph node metastasis. Methods: From January 2014 to September 2019, 78 patients with PTC who were treated in our hospital were selected for study. All subjects were divided into the metastatic group (42 cases) and the non-metastatic group (36 cases) according to cervical lymph node metastasis. The ultrasonographic image characteristics of the two groups were compared, and the sensitivity, specificity and accuracy of ultrasonographic diagnosis of PTC cervical lymph node metastasis were analyzed. In addition, the color doppler ultrasound blood flow parameters of the two groups were compared, the correlation between color doppler ultrasound blood flow parameters and lymph node metastasis was analyzed. Results: The proportion of lymphatic hilum and aspect ratio ≥ 2 in the metastatic group were lower than those in the non-metastatic group, while the proportion of calcification and cystic degeneration were higher than those in the non-metastatic group (all P<0.05). With pathological diagnosis as the gold standard, the sensitivity, specificity and accuracy of ultrasonic diagnosis of PTC cervical lymph node metastasis were 95.24%, 97.22% and 96.15%, respectively. There was no significant difference in acceleration time (AT) between the metastatic group and the non-metastatic group (P>0.05). Peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI) in the metastatic group were all higher than those in the non-metastatic group (all P<0.05). Pearson correlation analysis showed that PSV, PI and RI were positively correlated with lymph node metastasis (all P<0.05). Conclusion: Ultrasonography in diagnosis of PTC cervical lymph node metastasis is of high clinical value, and its blood flow parameters are closely related to lymph node metastasis. Detection of blood flow parameters is helpful to determine lymph node metastasis in patients with PTC. [ABSTRACT FROM AUTHOR]

Objective: Thyroglobulin antibodies (TgAb) are detected in thyroid cancer patients up to 25%. We investigated the prognostic value of TgAb positivity in patients with papillary thyroid carcinoma (PTC) after initial therapy.Patients and Methods: A database of 109 consecutive patients who underwent total thyroidectomy and therapeutic lateral neck dissection followed by remnant ablation for PTC between January 1989 and December 2014 was reviewed We recorded the patients' all serum Tg and TgAb levels over time to establish changing trends. Patients were classified as either positive or negative according to serum TgAb levels. The recurrence or persistence rates in both groups were compared.Results: Of the 109 patients enrolled 14 patients had TgAb positivity. Thirty-two (29.3%) showed disease recurrence or persistent disease during 101 months of follow-up. Twenty-seven of 95 patients (28.4%) with negative TgAb had persistent or recurrent disease, whereas 5 of 14 patients (35.7%) with positive TgAb had persistence or recurrence (P = 0.57). No significant difference in disease-free survival (115.3 ± 10.8 vs. 224.1 ± 16.6 months, P = 0.78) and overall survival (P = 0.59) was observed between TgAb positive and TgAb negative patients.Conclusions: TgAb status is not useful as a prognostic and predictive factor for clinical outcomes in patients with PTC in our experience. [ABSTRACT FROM AUTHOR]

Since Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) was introduced as a new thyroid tumour entity, many studies, and meta-analyses on diagnosing NIFTP have been published. NIFTP-revised histopathological criteria emerged in 2018. NIFTP is defined as a histological entity and its diagnosis requires a careful histological examination. Its molecular profile is similar to follicular-like tumours. Ultrasound features are unable to differentiate NIFTP. NIFTP is not a cytological diagnosis, but it influences the risk of malignancy in several categories of The Bethesda System for Reporting Thyroid Cytopathology terminology.

As a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed to identify the expression patterns of SIX1 and its co-activator EYA1. Papillary thyroid cancer cell lines, BCPAP, and TPC-1 cells were used to investigate the potential mechanism of SIX1 in vitro and in vivo. Flow cytometry analysis, MTT assay, the growth curve assay, colony formation assay, EdU incorporation and xenograft assay were performed to demonstrate the role of SIX1 in the malignant change of PTC cells. Western blot and Real-time PCR were used to detect the interaction among the SIX1, EYA1, and STAT3 signaling. In comparison with normal tissue, high expressions of SIX1 and EYA1 were associated with a malignant tumor. Importantly, SIX1 strongly correlated with EYA1 in thyroid carcinoma tissue microarray. Functional assays indicated SIX1 increased EYA1 expression by stabilizing EYA1 at the post-transcriptional level. Besides, SIX1 promoted the proliferation and invasion of thyroid carcinoma via activation of STAT3 signaling and its downstream targets in an EYA1-dependent manner. SIX1 can integrate with EYA1 to contribute to PTC development via activation of the classical STAT3 signaling. These data suggested targeting the abnormal activation of the SIX1/EYA1 complex may represent a novel therapeutic strategy for advanced PTC patients.

The aim of the present study was to investigate the effect of Forkhead box transcription factor M1 (FoxM1)-silencing on the growth, migration and invasion of K1 human papillary thyroid carcinoma (PTC) cells. The effect of FoxM1-small interfering RNA (siRNA) in K1 cells was detected by western blot analysis. FoxM1-siRNA and control siRNA were transfected into K1 cells using Lipofectamine® 2000 (transfection group, T) and the non-meaning sequence group (NM). K1 cells exposed to PBS solution comprised the blank control group (CON). Cell proliferation ability was detected using an MTT assay. Cell migration and invasion was detected by the single cell scratch test and Transwell invasion assay, respectively. Western blot analysis indicated that FoxM1 siRNA downregulated the expression of FoxM1 protein. Cell proliferation, migration and invasion were significantly lower in the T group compared with the NM and CON groups (P<0.05). These results indicated that silencing of FoxM1 expression could block growth, invasion and migration of K1 cells. This study may provide a novel target gene for targeted therapy of PTC. [ABSTRACT FROM AUTHOR]

As a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed to identify the expression patterns of SIX1 and its co-activator EYA1. Papillary thyroid cancer cell lines, BCPAP, and TPC-1 cells were used to investigate the potential mechanism of SIX1 in vitro and in vivo. Flow cytometry analysis, MTT assay, the growth curve assay, colony formation assay, EdU incorporation and xenograft assay were performed to demonstrate the role of SIX1 in the malignant change of PTC cells. Western blot and Real-time PCR were used to detect the interaction among the SIX1, EYA1, and STAT3 signaling. In comparison with normal tissue, high expressions of SIX1 and EYA1 were associated with a malignant tumor. Importantly, SIX1 strongly correlated with EYA1 in thyroid carcinoma tissue microarray. Functional assays indicated SIX1 increased EYA1 expression by stabilizing EYA1 at the post-transcriptional level. Besides, SIX1 promoted the proliferation and invasion of thyroid carcinoma via activation of STAT3 signaling and its downstream targets in an EYA1-dependent manner. SIX1 can integrate with EYA1 to contribute to PTC development via activation of the classical STAT3 signaling. These data suggested targeting the abnormal activation of the SIX1/EYA1 complex may represent a novel therapeutic strategy for advanced PTC patients. [ABSTRACT FROM AUTHOR]