OBJECTIVES: Lymph node metastasis in papillary thyroid cancer (PTC) is closely associated with tumor recurrence and patient survival. However, current technologies have limited sensitivity in detecting occult cervical lymph node metastases. Identifying accurate molecular markers for predicting PTC metastasis holds significant clinical value. This study aims to analyze WNT10A expression in PTC and its clinical significance, and to explore the role of WNT10A gene knockdown in PTC cell proliferation, invasion, and metastasis. METHODS: The expression of WNT10A in thyroid carcinoma was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and University of Alabama at Birminghara Cancer data analysis Portal (UALCAN) databases. Real-time RT-PCR was used to measure WNT10A mRNA levels in tumor and adjacent normal tissues from 32 PTC patients. Immunohistochemistry was conducted on 158 PTC specimens to assess WNT10A protein expression and its correlation with clinicopathological features. In vitro experiments were performed using K1 and TPC-1 cell lines. Cell proliferation was assessed using the Celigo system and methyl thiazolyl tetrazolium (MTT) assays; apoptosis was measured via flow cytometry; invasion and metastasis were evaluated using scratch and Transwell assays. A xenograft model was established in nude mice to observe tumor growth, and tumor weight and volume were compared between cell lines. Differentially expressed genes regulated by WNT10A were identified via mRNA sequencing, followed by Gene Ontology (GO) and ingenuity pathway analysis (IPA). Real-time PCR and Western blotting were used to validate the effects of WNT10A on key downstream mRNA and protein in the Tec kinase signaling pathway. RESULTS: WNT10A mRNA expression was significantly higher in thyroid cancer tissues compared to adjacent normal tissues according to GEPIA and UALCAN (both P<0.01). The real-time RT-PCR result showed that WNT10A mRNA expression in PTC tissues was high than that in adjacent tissues (P<0.01). Immunohistochemistry revealed significantly higher WNT10A protein expression in PTC tissues compared to adjacent tissues (P<0.01), and its expression correlated with multifocality, extrathyroidal invasion, and lymph node metastasis. WNT10A knockdown significantly inhibited proliferation, altered cell cycle distribution, and increased apoptosis in K1 and TPC-1 cells (all P<0.01). WNT10A silencing also reduced migration and invasion abilities in both cell lines. In vivo, WNT10A knockdown in TPC-1 cells suppressed tumor formation in nude mice. GO analysis and IPA suggested that the Tec kinase signaling pathway was a key downstream target of WNT10A. RT-PCR and Western blotting confirmed that WNT10A knockdown downregulated the expression of key genes (STAT3, MAPK8, TNFRSF21, and AKT2) in this pathway. CONCLUSIONS WNT10A is highly expressed in PTC and is associated with tumor proliferation, invasion, and metastasis. Its tumor-promoting effects may be mediated through suppression of the Tec kinase signaling pathway.
Humans ; Cell Proliferation ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/metabolism* ; Animals ; Wnt Proteins/metabolism* ; Neoplasm Invasiveness ; Mice ; Cell Line, Tumor ; Female ; Male ; Mice, Nude ; Apoptosis ; Lymphatic Metastasis ; Middle Aged ; Cell Movement ; Adult

Objective: Intrathyroid thymic carcinoma（ITTC） is a rare thyroid tumor that lacks typical clinical manifestations and imaging features, making preoperative diagnosis challenging.The primary treatment for ITTC is radical surgery; however, the effectiveness of adjuvant radiotherapy and chemotherapy post-surgery is not well-established. This paper presents a case of ITTC , analyzing the clinical data and correlating it with the literature to explore the clinical manifestations, diagnostic approach, treatment, and prognosis of ITTC.
Humans ; Prognosis ; Thymoma ; Thymus Neoplasms/diagnosis* ; Thyroid Neoplasms/pathology*

Objective:To observe the clinical progression of low-risk papillary thyroid microcarcinoma（LR-PTMC）, analyze the influencing factors of its oncological outcomes, and explore the feasibility of active surveillance（AS） of LR-PTMC. Methods:This study adopted a prospective observational research design. A total of 85 subjects diagnosed with LR-PTMC during health checkup in Health Management Center of our hospital from March 2021 to October 2022 were enrolled as the research subjects, for at least 2 years of AS follow-up observation. The clinical progress and oncological outcomes were recorded, disease progression was defined as any increase in nodule diameter ≥3 mm or the appearance of new lesions or lymph node metastasis or distant metastasis, and the oncological outcome was use disease progression defining. Cox proportional hazards regression model was used to analyze the influencing factors of oncological outcomes in LR-PTMC patients. Results:A total of 85 LR-PTMC patients who underwent physical examinations were included in this study. The median follow-up time was 2 years, and a total of 23 patients（27.06%） experienced disease progression. Among them, 18 patients（21.18%） had enlarged lesions（any nodule diameter increased by ≥3 mm）, and 5 patients（5.88%） had abnormal or metastatic cervical lymph nodes. The 2-year cumulative disease progression rate was 9.41%. The incidence age of LR-PTMC patients was younger, with a higher proportion of ≤45 years old. The proportion of baseline nodules with a maximum diameter greater than 5 mm is higher, and the proportion of baseline TPO Ab positivity was higher. Ultrasound showed a higher proportion of microcalcifications compared to the non progression group, and the differences were statistically significant（all P<0.05）. Multivariate Cox proportional hazards regression analysis showed that age of onset ≤45 years RR 95% CI 1.052（1.018-1.088） and ultrasound showing microcalcifications RR 95% CI 3.361（1.379-8.194） were independent risk factors affecting disease progression during AS in LR-PTMC patients（P<0.05）. Conclusion:Most LR-PTMC patients maintain stable lesion size and low lymph node metastasis rate during the AS process, with good oncological outcomes in the short term. AS can be considered as a safe and effective alternative to surgical treatment for LR-PTMC patients. But for patients with onset age ≤45 years and microcalcifications, the follow-up interval can be shortened for close observation.
Humans ; Thyroid Neoplasms/pathology* ; Disease Progression ; Prospective Studies ; Carcinoma, Papillary/pathology* ; Female ; Male ; Middle Aged ; Adult ; Watchful Waiting ; Lymphatic Metastasis ; Proportional Hazards Models ; Risk Factors

OBJECTIVES: To investigate the expression of apolipoprotein C1 (APOC1) in papillary thyroid carcinoma (PTC) and its effects on proliferation and apoptosis of PTC cells. METHODS: The expression level of APOC1 in PTC and its impact on prognosis were analyzed using GEPIA 2 and Kaplan-Meier databases. Immunohistochemistry (IHC) and Western blotting were used to detect the expression of APOC1 in PTC and adjacent tissues and in 3 PTC cell lines and normal thyroid Nthyori 3-1 cells. In TPC-1 and BCPAP cells, the effect of Lipofectamine 2000-mediated transfection with APOC1 siRNA or an APOC1-overexpressing plasmid on cell growth and colony formation ability were examined by observing the growth curves and using colony-forming assay. The changes in cell cycle and apoptosis of the transfected cells were analyzed with flow cytometry. RT-qPCR and Western blotting were used to detect the changes in expressions of P21, P27, CDK4, cyclin D1, Bcl-2, Bax, caspase-3 and caspase-9 and the key proteins in the JAK2/STAT3 signaling pathway. RESULTS: APOC1 expression was significantly higher in PTC tissues and the 3 PTC cell lines than in the adjacent tissues and Nthyori 3-1 cells, respectively. In TPC-1 and BCPAP cells, APOC1 knockdown obviously reduced cell proliferative activity, increased the percentage of G0/G1 phase cells, lowered the percentages of S and G2 phase cells, promoted cell apoptosis, and downregulated mRNA and protein expression levels of CDK4, cyclin D1 and Bcl-2 and the protein levels of p-JAK2 and p-STAT3. APOC1 overexpression in the cells produced the opposite effects on cell proliferation, apoptosis, cell cycle and the mRNA and protein expressions. The application of AG490, a JAK2 inhibitor, strongly attenuated APOC1 overexpression-induced activation of the JAK2/STAT3 signaling pathway in BCPAP cells. CONCLUSIONS APOC1 overexpression promotes proliferation and inhibits apoptosis of PTC cells possibly by activating the JAK2/STAT3 signaling pathway and accelerating cell cycle progression.
Humans ; Apoptosis ; Cell Proliferation ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Janus Kinase 2/metabolism* ; Thyroid Neoplasms/pathology* ; Thyroid Cancer, Papillary ; Cell Line, Tumor ; Carcinoma, Papillary

Thermal ablation has proven an effective treatment modality for certain thyroid diseases. However, its indications remain the subject of significant debate both domestically and internationally. Over recent years, several international academic organizations have issued consensus statements, position papers, and guidelines concerning thyroid thermal ablation. In China, the Chinese College of Interventionalists (CCI), in collaboration with other relevant academic organizations, released the "Expert consensus on thermal ablation for thyroid benign nodes, microcarcinoma and metastatic cervical lymph nodes (2018 edition)". This consensus statement received widespread recognition within the field and contributed significantly to the standardization of thyroid thermal ablation therapy in China. With the continuous accumulation of evidence-based medical data, the need for a more stringent and standardized approach to thyroid thermal ablation has become evident. Accordingly, the Interventional Ultrasound Committee of the CCI, in collaboration with multiple academic organizations and experts, conducted extensive discussions and multiple revisions before finalizing the "Multidisciplinary expert consensus on thermal ablation for benign thyroid diseases, low-risk thyroid carcinoma, and metastatic cervical lymph nodes (2025 edition)". This updated consensus builds on the framework of the 2018 edition, refining indications and contraindications, emphasizing standardized treatment, and outlining future directions for research and clinical applications of thyroid thermal ablation technology.
Humans ; Thyroid Neoplasms/surgery* ; Consensus ; Lymphatic Metastasis ; Lymph Nodes/pathology* ; Thyroid Diseases/surgery*

Objective To investigate the value of the novel lymphatic contrast-enhanced ultrasound(LCEUS)and conventional venous contrast-enhanced ultrasound(VCEUS)in the differential diagnosis of benign and malignant cervical lymph nodes in patients with thyroid cancer. Methods Patients with suspected thyroid cancer underwent conventional ultrasound,VCEUS,and LCEUS examinations of cervical lymph nodes before biopsy.The diagnostic abilities of conventional ultrasound,VCEUS,and LCEUS were compared with pathological results as the golden standard. Results Forty-four patients with 52 lymph nodes were included in the final data.Thirty-eight metastatic lymph nodes were confirmed by pathological results,and 14 were benign.The diagnostic sensitivity,specificity,and accuracy were 97.37%,71.43%,and 90.38% for LCEUS,92.11%,35.71%,and 76.92% for VCEUS,and 94.74%,21.43%,and 75.00% for conventional ultrasound,respectively.The area under the curve of LCEUS analyzed by the receiver operating characteristic curve was greater than that of VCEUS(P=0.020)and conventional ultrasound(P<0.001). Conclusion LCEUS could significantly improve the differential diagnosis of cervical lymph node metastasis in the patients with thyroid cancer,providing a basis for precise clinical treatment.
Humans ; Thyroid Neoplasms/diagnostic imaging* ; Lymphatic Metastasis/diagnostic imaging* ; Diagnosis, Differential ; Female ; Male ; Middle Aged ; Ultrasonography ; Adult ; Lymph Nodes/pathology* ; Contrast Media ; Neck ; Aged ; Young Adult ; Adolescent ; Sensitivity and Specificity

Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
Mice ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Mice, Nude ; Epithelial-Mesenchymal Transition ; Thyroid Neoplasms/pathology* ; Extracellular Vesicles/pathology* ; Mesenchymal Stem Cells ; Transcription Factors, TFIII/metabolism* ; Neoplastic Stem Cells/pathology*

Objective:To investigate the correlation between preoperative platelet parameters and the clinicopathological features of differentiated thyroid cancer. Methods:We retrospectively analyzed the medical records of patients with thyroid tumors admitted to Zhongda Hospital affiliated to Southeast University and healthy adults with normal physical examination results in our hospital from January 2019 to December 2020, and collected their general information and preoperative blood routine data. Patients with undifferentiated thyroid cancer, diabetes, coronary heart disease, hematological diseases, kidney diseases, autoimmune diseases, genetic diseases, infectious diseases, other systemic tumors, hepatitis or cirrhosis, or those taking anticoagulants were excluded. The exclusion criteria for healthy adults were the absence of the above diseases and normal physical examination results. Differences in platelet parameters among the three groups were compared, and the correlation between clinicopathological characteristics of thyroid cancer, accompanying cervical lymph node metastasis, and platelet parameters of patients was analyzed. A multivariate logistic regression model was used to analyze the risk factors of thyroid cancer with cervical lymph node metastasis. Results:A total of 117 cases of differentiated thyroid cancer were collected, including 33 males and 84 females, with an average age of （41.64±12.25） years; 46 patients had benign thyroid tumors, including 15 males and 31 females, with an average age of （41.35±12.52） years; 50 healthy adults with normal physical examination results in our hospital during the same period were also included, including 18 males and 32 females, with an average age of（42.02±9.62） years, without underlying diseases. The platelet count of the differentiated thyroid cancer group was higher than that of the benign thyroid tumor group（t=-2.219, P=0.028） and the normal control group（t=2.069, P=0.04）, while the platelet distribution width of the differentiated thyroid cancer group was lower than that of the benign thyroid tumor group（t=2.238, P=0.027） and the normal control group（t=-2.618, P=0.002）. These differences were statistically significant. Preoperative age ≤45 years（χ²=4.225, P=0.04）, tumor diameter>1 cm（χ²=4.415, P=0.036）, PLT（t=-4.018, P<0.01） increase, and PDW（t=4.568, P<0.01） decrease were significantly correlated with cervical lymph node metastasis of thyroid cancer and had statistical significance. Univariate analysis showed that age ≤45 years（OR=0.447, 95%CI 0.206-0.970, P=0.042）, tumor diameter>1 cm（OR=2.3, 95%CI 1.050-5.039, P=0.037）, PLT（OR=1.012, 95%CI 1.005-1.019, P=0.001）, and PDW（OR=0.693, 95%CI 0.518-0.827, P<0.01） were risk factors for cervical lymph node metastasis of thyroid cancer. The results of multifactorial logistic regression analysis showed that PLT（OR=1.008, 95%CI 1.001-1.016, P=0.026） and PDW（OR=0.692, 95%CI 0.564-0.848, P<0.01） were independent risk factors for thyroid cancer with cervical lymph node metastasis. Conclusion:PLT and PDW may be useful predictive factors for the differentiation of thyroid cancer malignancy and central lymph node metastasis.
Adult ; Male ; Female ; Humans ; Middle Aged ; Lymphatic Metastasis/pathology* ; Retrospective Studies ; Thyroid Neoplasms/surgery* ; Neck/pathology* ; Lymph Nodes/pathology* ; Adenocarcinoma

BACKGROUND: Previous studies have revealed that the number of cancer survivors developing a second primary malignancy is increasing, especially among thyroid cancer patients, and lung cancer is still the main cause of cancer death. Therefore, we aimed to investigate the risk of second primary lung cancer (SPLC) in patients with thyroid cancer. METHODS: We searched the PubMed, Web of Science, Embase, and Scopus databases up to November 24, 2021, for relevant research and merged the standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) to evaluate the risk of developing SPLC in patients with thyroid cancer. RESULTS: Fourteen studies involving 1,480,816 cases were included in our meta-analysis. The pooled result demonstrated that thyroid cancer patients may have a higher risk of SPLC than the general population (SIR = 1.21, 95% CI: 1.07-1.36, P  < 0.01, I2  = 81%, P  < 0.01). Subgroup analysis stratified by sex indicated that female patients may have a markedly higher risk of SPLC than male patients (SIR = 1.65, 95% CI: 1.40-1.94, P  < 0.01, I2  = 75%, P  < 0.01). CONCLUSIONS: Thyroid cancer patients are more likely to develop SPLC than the general population, especially women. However, other risk factors must be investigated, and more prospective studies are needed to confirm our results. REGISTRATION International Prospective Register of Systematic Reviews: No. CRD42021285399.
Humans ; Male ; Female ; Neoplasms, Second Primary/pathology* ; Systematic Reviews as Topic ; Lung Neoplasms/pathology* ; Risk Factors ; Thyroid Neoplasms/complications* ; Incidence

Humans ; Biopsy, Fine-Needle ; Consensus ; Thyroid Neoplasms/pathology* ; Thyroid Nodule/pathology* ; Sensitivity and Specificity