Background:The prevalence of thyroid carcinoma is on the rise, with cervical lymph node metastasis being a frequent occurrence necessitating surgical intervention. Chyle fistula, a significant postoperative complication, can have a substantial impact on recovery. Objective:To reduce the incidence of chyle fistula, enhance the effectiveness of postoperative treatment, and assist thyroid surgeons in performing cervical lymph node dissection, the consensus was compiled in a standardized and secure manner. Methods:Drawing from the expertise of Chinese specialists in managing chyle fistula and the latest international advancements in this field following cervical lymph node dissection, the thyroid tumor experts group of Chinese Thyroid Association, Chinese College of Surgeons, Chinese Medical Doctor Association and Thyroid Disease Professional Committee of Chinese Research Association have developed innovative approaches to address this issue. An evidence-based approach was employed, integrating the knowledge and practical experience of the panelists. Results:We developed twelve expert consensus recommendations, addressing the prevention, diagnosis, and treatment of postoperative chyle fistula. These recommendations included the dietary management and nutritional support, continuous negative pressure suction, local adhesive treatment, application of local compression methods, the use of somatostatin and its analogs, and surgery treatment. Conclusion:This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the management of chyle fistula.

Background: Data regarding the long-term recurrence in patients with intermediate-risk papillary thyroid carcinoma (PTC) are limited. The aim of this study was to assess the impact of primary tumor-related risk factors and lymph node (LN)-only risk factors on recurrence-free survival (RFS) in patients with intermediate-risk PTC. Materials and methods: Patients with PTC who received initial treatment at our institution between 2010 and 2016 were retrospectively reviewed. A total of 799 intermediate-risk PTC patients were included and further categorized into subgroups according to the different categories of intermediate-risk factors. The RFS rates of these subgroups were investigated and compared. Results: Structural recurrence developed in 11 patients (1.4%) of the whole cohort during a median follow-up duration of 96 months. There were no significant differences in RFS between the primary tumor-only risk group and the LN-only risk group, while the combined group of primary tumor risk factors and LN risk factor (metastatic LNs >5) was associated with a worse RFS rate. In the matched-pair analysis, no significant difference in RFS was found between patients who underwent thyroid lobectomy and those who underwent total thyroidectomy (6-year RFS: 99.6 vs. 98.8%, P=0.316) during a median follow-up duration of 100 months. Conclusions: Intermediate-risk PTC patients who underwent thyroid lobectomy had a comparable RFS to those who underwent total thyroidectomy. The combination of primary tumor risk factors and LN risk factor (metastatic LNs >5) may be a useful tool for predicting the risk of long-term structural recurrence in patients with intermediate-risk PTC.

INTRODUCTION:Lobectomy (LT) is not generally recommended for papillary thyroid cancer (PTC) patients with intermediate-risk features, although there is no high-level evidence showing that this approach is inferior. This study aimed to examine the association between the extent of thyroidectomy and the outcomes of intermediate-risk PTC patients. METHODS:Using the Surveillance, Epidemiology, and End Results database data (2004-2020), 8543 intermediate-risk PTC patients were stratified into LT and total thyroidectomy (TT) groups. Propensity score matching generated 1557 matched pairs. Cancer-specific survival (CSS) was analyzed via Kaplan-Meier and Cox regression. RESULTS:No significant CSS difference emerged between LT and TT in original (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.82-3.74, P = 0.144) or propensity score matching cohorts. Subgroup analyses confirmed comparable CSS for patients aged ≥55 y (HR = 1.55, 95% CI = 0.64-3.78, P = 0.327), tumors >40 mm (HR = 5.24, 95% CI = 0.69-39.87, P = 0.074), and lymph node metastasis (HR = 1.15, 95% CI = 0.42-3.09, P = 0.788). CONCLUSIONS:TT was not associated with a CSS advantage for PTC patients with intermediate-risk features.

Background::Cytopathology cannot be used to reliably distinguish follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), the second most common form of thyroid cancer, because they exhibit nearly identical cellular morphology. Given the challenges in diagnosis and treatment, this study aims to identify the mechanisms underlying FTC.Methods::Using parallel reaction monitoring-mass spectrometry (PRM-MS) assays, we identified and quantified 94 differentially expressed protein candidates from a retrospective cohort of 1085 FTC and FTA tissue samples from 18 clinical centers. Of these targeted proteins, those with the potential for distinguishing FTC from FTA were prioritized using machine learning. Co-immunoprecipitation (co-IP) and immunofluorescence co-localization assays, as well as gene interference, overexpression, and immunohistochemistry (IHC) experiments, were used to investigate the interactions and cellular functions of selected proteins.Results::Using machine learning models and feature selection methods, 30 of the 94 candidates were prioritized as key proteins. Co-IP and immunofluorescence co-localization assays using FTC cell lines revealed interactions among insulin-like growth factor 2 receptor (IGF2R), major vault protein (MVP), histone deacetylase 1 (HDAC1), and histone H1.5 (H1-5). Gene interference and overexpression experiments in FTC-133 cells confirmed the promotional role of these proteins in cell proliferation. IHC assays of patient samples further confirmed elevated expression of these four proteins in FTC compared with that in FTA.Conclusions::Our findings underscore the utility of advanced proteomic techniques in elucidating the molecular underpinnings of FTC, highlighting the potential significance of IGF2R, MVP, HDAC1, and H1-5 in FTC progression, and providing a foundation for the exploration of targeted therapies.

DNA damage repair (DDR) is essential for cancer cell survival and treatment resistance, making it a critical target for tumor therapy. The eukaryotic AAA+ adenosine triphosphatase valosin-containing protein (VCP), which is transported from the cytoplasm into the nucleus, plays a critical role in the DDR process. However, the nuclear translocation and molecular mechanism of VCP for DDR remain elusive. Here, we define VCP as a KPNB1 interacting protein through a combination of chemical and immunoprecipitation mass spectrometry approaches. Further biochemical studies elucidate that KPNB1 directly transports VCP into the nucleus. We also identify withaferin A (WA) as a small molecule that can retard VCP nuclear localization via covalent binding to CYS 158 of KPNB1. Further studies verify WA as an effective antitumor drug candidate via blocking VCP nuclear localization to impact on the DDR pathway in vivo. Our findings underly the unclear VCP's role in DDR in a KPNB1-dependent manner and provide an important theoretical basis for developing small-molecule inhibitors targeting this process.

Differentiating follicular thyroid adenoma (FTA) from carcinoma (FTC) remains challenging due to similar histological features separate from invasion. This study developed and validated DNA- and/or protein-based classifiers. A total of 2443 thyroid samples from 1568 patients were obtained from 24 centers in China and Singapore. Next-generation sequencing of a 66-gene panel revealed 41 (62.1%) detectable genes, while 25 were not, showing similar alteration patterns with differing mutation frequencies. Proteomics quantified 10,336 proteins, with 187 dysregulated. A discovery protein-based XGBoost model achieved an AUROC of 0.899 (95% CI, 0.849-0.949), outperforming the gene-based model (AUROC 0.670 [95% CI, 0.612-0.729]). A subsequent 24-protein classifier, developed via targeted mass spectrometry and validated in three independent sets, showed high performance in retrospective cohorts (AUROC 0.871 [95% CI, 0.833-0.910] and 0.853 [95% CI, 0.772-0.934]) and prospective biopsies (AUROC 0.781 [95% CI, 0.563-1.000]). It exhibited a 95.7% negative predictive value for ruling out malignancy. This study presents a promising protein-based approach for the differential diagnosis of FTA and FTC, potentially enhancing diagnostic accuracy and clinical decision-making.

Objective Parathyroid autotransplantation is common in thyroid surgery. However, there is still no special preservation solution for the parathyroid. Therefore, the main purpose of our study is to explore the preservation effect of new parathyroid preservation solution developed by our institution. Methods In the first part, retrieved parathyroids of new parathyroid preservation solution, Celsior preservation solution, HTK solution, normal saline, blank control and the muscle preservation were observed by HE staining and electron microscope. In the second part, retrieved parathyroids were preserved in preservation solution and then autotransplantation was performed. After 1 month, the cell structure and morphological changes of organelles were observed under light microscope and electron microscope. The central arterial blood of rabbit ear was collected 1 day before surgery, 1 day, 14 days and 30 days after surgery to detect the changes of Ca and PTH levels. Results Compared with new parathyroid preservation solution, Celsior preservation solution, HTK solution, normal saline, blank control and muscle preservation, the new parathyroid preservation solution had the best preservation effect in temporary preservation and could maintain cell morphology for up to 2 hours. (P<0.05) New parathyroid preservation solution group had the highest efficacy score, and the difference was not statistically significant compared with normal parathyroid. (P>0.05) During autotransplantation (lasted for 1 month), the retrieved parathyroids preserved by new parathyroid preservation solution still maintained similar cell morphology to normal parathyroids. The autotransplantation survival rate of new parathyroid preservation solution, Celsior preservation solution, HTK solution, normal saline, blank control and muscle preservation were 99.38%, 53.00%, 52.00%, 41.38%, 36.75%, 19.88%, respectively. Conclusion New parathyroid preservation solution can preserve retrieved parathyroids well, reduce cell edema and oxidative damage, and improve the survival rate of parathyroid autotransplantation.

Context Distant metastases are the primary cause of therapy failure and mortality in patients with papillary thyroid carcinomas (PTCs). However, the underlying mechanism responsible for the initiation of tumor cell dissemination and metastasis in PTCs has rarely been investigated.Objective The aim of this study was to investigate effects and underlying molecular mechanisms of circulating exosomal microRNAs (miRNAs) in distant metastatic PTCs.Methods The most relevant circulating exosomal miRNA to distant metastatic PTCs were verified between distant metastatic PTCs and nondistant metastatic PTCs by miRNA microarray, quantitative real-time polymerase chain reaction (qRT-PCR) assays and receiver operating characteristic (ROC) curves. The parental and recipient cells of that circulating exosomal miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of circulating exosomal miRNAs that contribute to the development of distant metastases.Results We determined that PTC-derived exosomal miR-519e-5p was significantly upregulated in the circulatory system in distant metastatic PTCs. Further tests demonstrated that PTC cells can acquire a more malignant phenotype via hnRNPA2B1-mediated sorting of tumor suppressor miR-519e-5p into exosomes to activate Wnt signaling pathway via upregulating PLAGL2. Furthermore, miR-519e-5p included in PTC-derived exosomes can be transferred to recipient CD8(+) T cells and aid in tumor immune escape in distant organs through inhibiting Notch signaling pathway by downregulating NOTCH2.Conclusion Our findings highlight the dual role of PTC-derived exosomal miR-519e-5p in distant metastasis, which may improve our understanding of exosome-mediated distant metastatic mechanisms.

BackgroundThermal ablation and conventional thyroidectomy are effective therapeutic methods for treating benign thyroid nodules (BTNs), but the psychological impacts of these methods in BTN patients are largely unknown.Materials and methodsThis survey study prospectively enrolled patients who were admitted to our hospital between July 2021 and July 2022. The four validated scales were applied to quantify psychological distress and sleep quality at five points (the day admitted to the hospital, the day discharged from the hospital, and 1, 3, and 6 months after treatment). Participants who were diagnosed with BTNs and completed the questionnaires were ultimately enrolled and divided into thermal ablation and conventional thyroidectomy groups. A propensity score matching (PSM) cohort was subsequently developed to evaluate longitudinal and cross-sectional changes in psychological-related indicators.ResultsAmong 548 eligible BTN patients, 460 patients completed all the questionnaires throughout the follow-up (response rate: 83.94%), including 368 (80.00%) patients who underwent thermal ablation and 92 (20.00%) patients who underwent conventional thyroidectomy. After PSM, a total of 342 patients were enrolled (256 patients underwent thermal ablation, and 86 patients underwent conventional thyroidectomy). The psychological-related indicators of patients in the thermal ablation group remained relatively stable during the 6-month follow-up, but patients in the conventional thyroidectomy group may have experienced greater anxiety and sleep quality concerns in the longitudinal assessment. Additionally, in the cross-sectional evaluation, the sleep quality of the thermal ablation group was also better than that of the conventional thyroidectomy group postoperatively.ConclusionsThermal ablation is superior to conventional thyroidectomy for BTN patients in terms of psychological-related indicators.

BackgroundThe clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis.MethodA total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival curve estimation and Cox proportional hazard regression were applied.ResultsOverall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients’ pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68–4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5 cm, and more invasive tumor extension were independent bad outcome predictors.ConclusionThe populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

To investigate the implications of Lobectomy (LT) or total thyroidectomy (TT) on psychological distress and sleep quality in PTC patients with a low to intermediate risk of recurrence and tumors measuring 1 to 4 cm. Patients who were admitted to our hospital between July 2021 and July 2022 were prospectively enrolled in this survey. Psychological distress and sleep quality were assessed at hospitalization, discharge, and 1, 3, and 6 months post-treatment using validated scales. Participants were divided into LT and TT groups, with propensity score matching (PSM) applied for analyses. Among 525 eligible PTC patients, 440 patients completed all the questionnaires throughout the follow-up. After PSM, 166 patients underwent LT, and 166 patients underwent TT were enrolled. The psychological distress and sleep quality of patients in the LT group remained relatively stable during the 6-month follow-up, but patients in the TT group may have faced greater sleep quality concerns in the longitudinal assessment. Additionally, the sleep quality of the TT group was also worse than that of the LT group postoperatively. The sleep quality rather than other psychological distress of patients with PTC with a low to intermediate risk of recurrence is associated with the extent of surgery.

Background The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. Methods This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. Results The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. Conclusions The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.

Background: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization classification of follicular thyroid carcinoma (FTC) are not well established. Material and Methods: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. CSS, the primary outcome, was compared among the 3 subtypes of patients with FTC before and after adjusting for differences using propensity score matching (PSM). The patients with FTC in different subtypes were then divided into 2 groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. Results: A total of 2433 patients with mi-FTC, 216 patients with ea-FTC, and 554 patients with wi-FTC were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (P = .805), which was better than that of patients with wi-FTC (P < .001; P = .021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (hazard ratio [HR], 1.21; 95% CI, .46-3.18; P = .705) or the wi-FTC PSM cohort (HR, 0.56; 95% CI, .35-1.08; P = .086). However, subgroup analysis demonstrated that patients with wi-FTC and N1 stage (HR, 0.44; 95% CI, .20-.99; P = .018) or M1 stage (HR, 0.25; 95% CI, .11-.53; P < .001) could gain CSS advantage from RAIT. Conclusion: The RAIT can provide a CSS advantage for patients with wi-FTC who with N1-stage or M1-stage disease.

BACKGROUND:Oncocytic carcinoma of the thyroid (OCA) is an independent type of thyroid cancer. Radioactive iodine (RAI) therapy was frequently administered to OCA patients, but its contribution to improving survival is indefinite. METHODS:4641 OCA patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied. RESULTS:Tumor size, SEER stage, primary surgery, and neck dissection were prognostic factors for cancer-specific survival. The results of competing risk analysis demonstrated that age over 55 years dramatically increased non-OCA death risks. Treatments that improve non-OCA survival (including total thyroidectomy, RAI therapy, and systemic therapy) should be recommended in OCA patients older than 55 years of age. Neck lymphadenectomy should not be recommended for OCA, since the metastatic lymph node ratio was low (about 3%). CONCLUSIONS:RAI therapy can improve survival in OCA by reducing noncancer death risks.

Background: Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Methods: Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) -18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer -specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. Results: The 5- and 10 -year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). Conclusions: PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

AbstractDifferentiating follicular thyroid adenoma (FTA) from carcinoma (FTC) remains challenging due to similar histological features separate from invasion. In this study, we aim to develop and validate DNA and protein-based classifiers for FTA/FTC differentiation. We collected 2443 samples from 1568 patients across 24 centers and applied next-generation sequencing, as well as discovery and targeted proteomics. Machine learning models were developed and compared utilizing DNA and/or protein features. The discovery protein-based model (AUC 0.899) outperformed the gene-based model (AUC 0.670). Consequently, we generated a protein-based model with targeted mass spectrometry and further validated it in three independent testing sets. The 24-protein-based model achieved high performance in the retrospective sets (AUC 0.871 and 0.853) and the prospective fine-needle aspiration biopsies (AUC 0.781). The classifier notably illustrated a 95.7% negative predictive value for ruling out malignant nodules. This study offers a promising protein-based approach for differential diagnosis of FTA and FTC.HighlightsGenetic and proteomic profiling of follicular thyroid tumors from 1568 patients across 24 centersAI model based on proteins (AUC 0.899) outperformed that based on gene mutations (AUC 0.670) for differentiation of FTA and FTCValidation of the protein model in two retrospective cohorts (AUCs: 0.871, 0.853) and a prospective (AUC 0.781)The protein model has 95.7% negative predictive value for ruling out malignant nodules

BackgroundMedullary thyroid cancer (MTC) is a challenging malignancy. The survival outcome of MTC based on AJCC staging system does not render a discriminant classifier among early stages.Methods3601 MTC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Smooth curve fitting, Cox proportional hazard regression and competing risk analysis were applied.ResultsA linear correlation between age and log RR (relative risk of overall death) was detected. Overlaps were observed between K-M curves representing patients aged 45–50, 50–55, and 55–60. The study cohort was divided into 3 subgroups with 2 age cutoffs set at 45 and 60. Each further advanced age cutoff population resulted in a roughly “5%” increase in MTC-specific death risks and an approximately “3 times” increase in non-MTC-specific death risks.ConclusionsThe survival outcome disparity across age cutoffs at 45 and 60 for MTC has been well defined.

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.

Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, has the worst prognosis, and lacks effective treatment in clinical practice. Thrombospondin-1 (THBS1) is a multifunctional extracellular matrix (ECM) glycoprotein that regulates cell proliferation, apoptosis, and metastasis, and is considered a potential clinical biomarker for the monitoring and prognostication of various tumors. However, the specific roles and molecular mechanisms of action of THBS1 in ATC remain unclear. In this study, we found that Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a THBS1 inhibitor, significantly inhibited ATC tumor growth both in vitro and in vivo. Mechanistically, we demonstrated that THBS1 was the target gene of PA-MSHA in ATC and identified the THBS1/FAK/AKT axis as the key antitumor signaling pathway. Furthermore, we confirmed that THBS1 was overexpressed in ATC tumors and that high levels of THBS1 were associated with a poorer prognosis in thyroid cancer. Silencing THBS1 significantly decreased p-FAK and p-AKT levels, resulting in significant inhibition of cell proliferation and apoptosis in ATC cells. These findings suggest that the THBS1/FAK/AKT axis is a promising therapeutic target for ATC treatment.