1.Expression of WNT10A in papillary thyroid carcinoma and its effect on cell proliferation, invasion, and metastasis.
Li YUAN ; Ping ZHOU ; Yongfeng ZHAO ; Jiale LI ; Yan ZHANG ; Wengang LIU
Journal of Central South University(Medical Sciences) 2025;50(3):402-415
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
2.High expression of apolipoprotein C1 promotes proliferation and inhibits apoptosis of papillary thyroid carcinoma cells by activating the JAK2/STAT3 signaling pathway.
Yu BIN ; Ziwen LI ; Suwei ZUO ; Sinuo SUN ; Min LI ; Jiayin SONG ; Xu LIN ; Gang XUE ; Jingfang WU
Journal of Southern Medical University 2025;45(2):359-370
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
3.Discussion on how to optimize active surveillance for low-risk papillary thyroid microcarcinoma in China.
Shuai XUE ; Pei Song WANG ; Qi Yu LU ; Guang CHEN
Chinese Journal of Surgery 2023;61(6):462-466
Active surveillance, as a first-line treatment strategy for low-risk papillary thyroid microcarcinoma, has been recommended by guidelines worldwide. However, active surveillance has not been widely accepted by doctors and patients in China. In view of the huge challenges faced by active surveillance, doctors should improve their understanding of the "low risk" of papillary thyroid micropapillary cancer, identify some intermediate or high-risk cases, be familiar with the criteria and methods of diagnosis for disease progression, and timely turn patients with disease progression into more active treatment strategies. By analyzing the long-term cost-effectiveness of active surveillance, it is clear that medical expense is only one cost form of medical activities, and the health cost (thyroid removal and surgical complications) paid by patients due to"over-diagnosis and over-treatment" is the most important. Moreover, the weakening of the patients' social function caused by surgical procedures is a more hidden and far-reaching cost. The formulation of health economic policies (including medical insurance) should promote the adjustment of diagnosis and treatment behavior to the direction which is conducive to the long-term life and treatment of patients, improving the overall health level of society and reducing the overall cost. At the same time, doctors should stimulate the subjective initiative of patients, help them fully understand the impact of various treatment methods on their psychological and physical status, support patients psychologically, and strengthen their confidence in implementing active surveillance. By strengthening multi-disciplinary treatment team and system support, doctors can achieve risk stratification of papillary thyroid microcarcinoma, accurate judgment of disease progress, timely counseling for psychological problems, and long-term adherence to active surveillance. Improving the treatment level of advanced thyroid cancer is the key point of improve the prognosis. It is important to promote the development of active surveillance for low-risk papillary thyroid microcarcinoma. In the future, it is necessary to carry out multi-center prospective research and accumulate research evidence for promoting the standardization process of active surveillance. Standardized active surveillance will certainly benefit specific papillary thyroid microcarcinoma patients.
Humans
;
Thyroidectomy/methods*
;
Prospective Studies
;
Watchful Waiting/methods*
;
Thyroid Neoplasms/pathology*
;
Disease Progression
;
Thyroid Cancer, Papillary/surgery*
4.A comparative study for the efficacies of transaxillary non-inflatable endoscopic surgery versus traditional surgery for papillary thyroid carcinoma.
Xiao Lei CHEN ; Chao LI ; Yu Qiu ZHOU ; Yong Cong CAI ; Yu Dong NING ; Chun Yan SHUI ; Xu WANG ; Zi Xun ZENG ; Gang QIN ; Ming Hua GE ; Chuan Ming ZHENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(4):351-357
Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ2=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.
Male
;
Female
;
Humans
;
Thyroid Cancer, Papillary/surgery*
;
Retrospective Studies
;
Quality of Life
;
Thyroid Neoplasms/pathology*
;
Endoscopy
;
Thyroidectomy/methods*
6.Effect of Calcification on the Ultrasound-Guided Radiofrequency Ablation of Papillary Thyroid Carcinoma.
Yi-Ming LI ; Lin YAN ; Jing XIAO ; Ming-Bo ZHANG ; Yu-Kun LUO
Acta Academiae Medicinae Sinicae 2023;45(5):803-808
Objective To investigate the effect of calcification on the ultrasound-guided radiofrequency ablation(RFA)of papillary thyroid carcinoma(PTC).Methods We retrospectively analyzed the preoperative and follow-up data of 164 patients(182 nodules)with PTC treated by percutaneous ultrasound-guided RFA in the First Medical Center of Chinese PLA General Hospital from January 1,2018 to December 31,2021.The tumor status 12 months after RFA was taken as the endpoint event.The univariate Logistic regression analysis was employed to predict the influencing factors of incomplete ablation.The factors were then included in the multivariate Logistic regression analysis for prediction of the independent risk factors of incomplete ablation.Results The maximum nodule diameter(OR=1.16,95%CI=1.04-1.29,P=0.009)and calcification ratio >2/3(OR=19.27,95%CI=4.02-92.28,P<0.001)were the factors influencing the disappearance of lesion 12 months after RFA.Conclusions PTC with calcification can be treated with ultrasound-guided RFA.In the case of calcification ratio ≤ 2/3,this therapy demonstrates the effect equivalent to that of no calcification.
Humans
;
Thyroid Cancer, Papillary/surgery*
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Radiofrequency Ablation/methods*
;
Calcinosis
;
Thyroid Neoplasms/pathology*
;
Ultrasonography, Interventional
8.Analysis of risk factors for recurrence of differentiated thyroid carcinoma after surgical resection combined with iodine-131 and TSH suppression therapy.
Ting YE ; Shengwei LAI ; Baolin CAO ; Baixuan XU ; Ruimin WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(5):370-374
Objective:To investigate the risk factors of recurrence after surgical resection of differentiated thyroid carcinoma combined with iodine-131 and TSH(Thyroid stimulating hormone) inhibition therapy. Methods:From January 2015 to April 2020, the clinical data of patients with structural recurrence and without recurrence were retrospectively collected after surgical treatment combined with iodine-131 and TSH inhibition therapy in the First Medical Center of PLA General Hospital. The general conditions of the two groups of patients were analyzed and the measurement data in line with the normal distribution was used for comparison between groups. For measurement data with non-normal distribution, the rank sum test was used for inter-group comparison. The Chi-square test was used for comparison between the counting data groups. Univariate and multivariate regression analyses were used to determine the risk factors associated with relapse. Results:The median follow-up period was 43 months(range 18-81 months) and 100 patients(10.5%) relapsed among the 955 patients. Univariate analysis showed that tumor size, tumor multiple, the number of lymph node metastases>5 in the central region of the neck, and the number of lymph node metastases>5 in the lateral region were significantly correlated with post-treatment recurrence(P<0.001, P=0.018, P<0.001, P<0.001). Multivariate analysis showed that tumor size(adjusted odds ratio OR: 1.496, 95%CI: 1.226-1.826, P<0.001), tumor frequency(adjusted odds ratio OR: 1.927, 95%CI: 1.003-3.701, P=0.049), the number of lymph node metastases in the central neck region>5(adjusted odds ratio OR: 2.630, 95%CI: 1.509-4.584, P=0.001) and the number of lymph node metastases in the lateral neck region>5(adjusted odds ratio OR: 3.074, 95%CI: 1.649-5.730, P=0.001) was associated with tumor recurrence. Conclusion:The study showed that tumor size, tumor multiple, the number of lymph node metastases in the central region of the neck>5 and the number of lymph node metastases in the side of the neck >5 are independent risk factors for recurrence of differentiated thyroid cancer after surgical resection combined with iodine-131 and TSH inhibition therapy.
Humans
;
Thyroid Cancer, Papillary/surgery*
;
Lymphatic Metastasis/pathology*
;
Retrospective Studies
;
Neck Dissection
;
Thyroidectomy/adverse effects*
;
Neoplasm Recurrence, Local/pathology*
;
Thyroid Neoplasms/surgery*
;
Risk Factors
;
Adenocarcinoma
;
Thyrotropin
;
Lymph Nodes/pathology*
9.Clinical significance of multigene assay in papillary thyroid carcinoma.
Yuan SHI ; Kai QIAN ; Kai GUO ; Jun LIU ; Zhuoying WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(5):375-379
Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma(PTC). Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients(P=0.023). TERT promotor-mutated tumors had a large diameter(P=0.019), a high proportion of multifocal lesions(P=0.050), and a large number of lymph node metastases(P=0.031). Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel(Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01). In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age(P=0.029) and tumor size(P<0.01) among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.
Humans
;
Male
;
Thyroid Cancer, Papillary/genetics*
;
Thyroid Neoplasms/pathology*
;
Proto-Oncogene Proteins B-raf/genetics*
;
Clinical Relevance
;
Carcinoma, Papillary/pathology*
;
Mutation
10.Papillary carcinoma in a thyroglossal duct remnant: a case report.
Jiao ZHOU ; Qiongling HUANG ; Ming LU ; Shuqiang CHU ; Yizheng ZHANG ; Chaohui ZHENG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(6):491-493
This case report has described a case of papillary carcinoma of thyroglossal duct in a young male. This patient was admitted with a mass in the anterior neck for 2 years. Preoperative Bultrasonography, CT and MR showed a subcutaneous cystic mass with irregular calcification shadow in the central region of the neck without obvious enhancement. Initial diagnosis was thyroglossal duct cyst, and was excised by Sistrunk under general anesthesia. The postoperative pathological examination showed thyroglossal duct cyst combined with thyroid papillary carcinoma, which was confirmed by immunohistochemistry as thyroglossal duct papillary carcinoma.
Humans
;
Male
;
Thyroid Neoplasms/surgery*
;
Carcinoma, Papillary/pathology*
;
Thyroglossal Cyst/surgery*
;
Thyroid Cancer, Papillary

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