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Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.
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Imagen Óptica , Glándulas Paratiroides , Espectroscopía Infrarroja Corta , Tiroidectomía , Humanos , Glándulas Paratiroides/cirugía , Glándulas Paratiroides/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Imagen Óptica/métodos , Adulto , Espectroscopía Infrarroja Corta/métodos , Adhesión en Parafina/métodos , Anciano , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Receptores Sensibles al Calcio/metabolismo , Receptores Sensibles al Calcio/análisisRESUMEN
Background: The prevalence of papillary thyroid cancer is gradually increasing and the trend of youthfulness is obvious. Some patients may not be able to undergo surgery, which is the mainstay of treatment, due to physical or financial reasons. Therefore, the prediction of cancer-specific survival (CSS) in patients with non-operated papillary thyroid cancer is necessary. Methods: Patients' demographic and clinical information was extracted from the Surveillance, Epidemiology, and End Results database. SPSS software was used to perform Cox regression analyses as well as propensity score matching analyses. R software was used to construct and validate the nomogram. X-tile software was used to select the best cutoff point for patient risk stratification. Results: A total of 1319 patients were included in this retrospective study. After Cox regression analysis, age, grade, T stage, M stage, radiotherapy, and chemotherapy were used to construct the nomogram. C-index, calibration curves, and receiver operating characteristic curves all verified the high predictive accuracy of the nomogram. The decision curve analysis demonstrated that patients could gain clinical benefit from this predictive model. Survival curve analysis after propensity score matching demonstrated the positive effects of radiotherapy on CSS in non-operated patients. Conclusion: Our retrospective study successfully established a nomogram that accurately predicts CSS in patients with non-operated papillary thyroid cancer and demonstrated that radiotherapy for operated patients can still help improve prognosis. These findings can help clinicians make better choices.
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Nomogramas , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Cáncer Papilar Tiroideo/mortalidad , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Adulto , Pronóstico , Anciano , Tasa de Supervivencia , Programa de VERF , Adulto JovenRESUMEN
OBJECTIVE: To create a formalized method for predicting papillary thyroid cancer recurrence after hemithyroidectomy based on preoperative data. MATERIAL AND METHODS: At this stage of the study, we selected 101 patients with papillary thyroid cancer who underwent surgical treatment in 2017-2023. Recurrence was observed in in 47 patients. Fifty-four patients had no recurrence within 5 years after surgical treatment, i.e. these patients underwent surgery in 2017-2018. To find prediction rules, we used original classification method based on searching for subsets of variables and piecewise linear rules separating classes in pairs with subsequent voting of such rules to make a decision. RESULTS: The exam was carried out using a training sample (101 cases) and sliding control method (10 tests on 10 random cases). On the training sample, sensitivity of predictive algorithm was 91%, specificity 78% and error rate 13%. The aggregated result of 10 trials using sliding control method revealed sensitivity of predictive algorithm 86%, specificity 75% and error rate 15%. This result is close to overall sample and confirms the effectiveness of this method for predicting recurrence. CONCLUSION: The pilot experiments revealed the patterns in data for potential prediction of recurrence based on preoperative indicators. Further study of this problem may be valuable for decision-making and adjustments in the management of patients with papillary thyroid cancer.
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Recurrencia Local de Neoplasia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Masculino , Femenino , Tiroidectomía/métodos , Persona de Mediana Edad , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Adulto , Algoritmos , Periodo PreoperatorioRESUMEN
Objective: This study aims to analyze the relationship between papillary thyroid carcinoma (PTC) and various factors. Methods: The study involved two groups-PTC patients and non-PTC controls. We utilized binary logistic regression and Least Absolute Shrinkage and Selection Operator (Lasso) regression for variable selection and risk factor analysis. Correlation analysis was performed using Spearman's rank correlation. The diagnostic value of thyroid stimulating hormone (TSH) levels for PTC was assessed using Receiver Operating Characteristic (ROC) curves. Results: PTC patients exhibited higher body mass index (BMI) (23.71 vs. 22.66, p<0.05) and TSH levels (3.38 vs. 1.59, p<0.05). Urinary iodine concentration (UIC) was an independent predictor of PTC (OR=1.005, p<0.05). The optimal TSH threshold for PTC diagnosis was 2.4 mIU/L [The Area Under the Curve (AUC)=67.3%, specificity=71.4%, sensitivity=70.1%]. TSH levels positively correlated with BMI (r=0.593, p<0.05) and UIC (r=0.737, p<0.05). Conclusions: UIC may be an independent predictor of PTC, and TSH levels have some diagnostic value for identifying PTC.
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Cáncer Papilar Tiroideo , Pruebas de Función de la Tiroides , Neoplasias de la Tiroides , Tirotropina , Humanos , Masculino , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/orina , Cáncer Papilar Tiroideo/sangre , Cáncer Papilar Tiroideo/epidemiología , Femenino , Factores de Riesgo , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/orina , Adulto , Tirotropina/sangre , Persona de Mediana Edad , Índice de Masa Corporal , Yodo/orina , Glándula Tiroides , Estudios de Casos y Controles , Curva ROCRESUMEN
SPRED3 (Sprouty-related EVH1 domain containing 3) mutants are depicted in various cancers, however, nothing is known about its biofunction in thyroid cancer (THCA). Bioinformatic analyses were conducted to ascertain the level of SPRED3 expression in THCA tissues and its importance in the prognosis of THCA patients. Flag-SPRED3 plasmid and SPRED3-knockout vector were developed to overexpress or deplete the SPRED3 expression in THCA cells. The function of SPRED3 on THCA cell proliferation was examined using the colony formation assay and CCK8 assay. The effect of SPRED3 expression on the transcriptional activity of NF-κB was also examined using luciferase reporter assays. High SPRED3 expression was associated with unfavorable clinical outcomes, advanced tumor characteristics, and traditional molecular markers of papillary thyroid cancer in THCA patients. Genetic analysis revealed differences in mutation rates in key genes between SPRED3-high and SPRED3-low THCA cases. It is also revealed that SPRED3 influenced the immune microenvironment, with increased stromal and immune scores and altered immune cell infiltration. Functionally, SPRED3 overexpression enhanced THCA cell viability and colony formation, while its depletion reduced cell growth and proliferation. In vivo experiments in mice confirmed the inhibitory effect of SPRED3 depletion on tumor growth. Mechanically, we found that SPRED3 activated the NF-κB signaling. For the first time, we found that SPRED3 promotes THCA cell proliferation via the NF-κB signaling pathway. This finding may provide insight into SPRED3's prognostic potential in thyroid cancer and provide the rationale for SPRED3-targeted druggable interventions.
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Proliferación Celular , FN-kappa B , Transducción de Señal , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , FN-kappa B/metabolismo , Animales , Ratones , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Masculino , Pronóstico , Microambiente Tumoral , Persona de Mediana Edad , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismoRESUMEN
Genetic alterations are well known to be related to the pathogenesis and prognosis of papillary thyroid carcinoma (PTC). Some miRNA expression dysregulations have previously been described in the context of cancer development including thyroid carcinoma. In our study, we performed original molecular diagnostics on tissue samples related to our own patients. We aimed to identify all dysregulated miRNAs in potential association with PTC development via sequencing much higher numbers of control-matched PTC tissue samples and analyzing a wider variety of miRNA types than previous studies. We analyzed the expression levels of 2656 different human miRNAs in the context of 236 thyroid tissue samples (118 tumor and control pairs) related to anonymized PTC cases. Also, KEGG pathway enrichment analysis and GO framework analysis were used to establish the links between miRNA dysregulation and certain biological processes, pathways of signaling, molecular functions, and cellular components. A total of 30 significant differential miRNA expressions with at least ±1 log2 fold change were found related to PTC including, e.g., miR-551b, miR-146b, miR-221, miR-222, and miR-375, among others, being highly upregulated, as well as miR-873 and miR-204 being downregulated. In addition, we identified miRNA patterns in vast databases (KEGG and GO) closely similar to that of PTC including, e.g., miRNA patterns of prostate cancer, HTLV infection, HIF-1 signaling, cellular responses to growth factor stimulus and organic substance, and negative regulation of gene expression. We also found 352 potential associations between certain miRNA expressions and states of clinicopathological variables. Our findings-supported by the largest case number of original matched-control PTC-miRNA relation research-suggest a distinct miRNA expression profile in PTC that could contribute to a deeper understanding of the underlying molecular mechanisms promoting the pathogenesis of the disease. Moreover, significant miRNA expression deviations and their signaling pathways in PTC presented in our study may serve as potential biomarkers for PTC diagnosis and prognosis or even therapeutic targets in the future.
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Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , MicroARNs , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Transducción de Señal/genética , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Redes Reguladoras de GenesAsunto(s)
Metástasis Linfática , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/secundario , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/secundario , Femenino , Ganglios Linfáticos/patología , Masculino , Carcinoma Papilar/patología , Persona de Mediana EdadRESUMEN
Purpose: The present study aimed to analyze and compare sonographic features of papillary thyroid carcinoma (PTC) subtypes to determine whether ultrasound (US) may aid in differentiating particular subtypes. Methods: This retrospective study enrolled 133 patients diagnosed with 142 histopathologically proven PTCs as per the fifth edition of the World Health Organization classification of thyroid neoplasms between January 2013 and May 2023. US features based on the American College of Radiology and European Thyroid Imaging and Reporting Data Systems (TIRADS), and histopathological characteristics of nodules were assessed and compared. Results: Histopathological analysis yielded 55 (38.7%) classic PTC, 32 (22.5%) invasive encapsulated follicular variant (IEFV) PTC, 20 (14.1%) oncocytic subtype, 14 (9.9%) non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 11 (7.8%) infiltrative follicular subtype, 7 (4.9%) tall cell subtype, 2 (1.4%) solid subtype, and 1 (0.7%) diffuse sclerosing subtype. The US findings indicating malignancy, such as taller-than-wide shape, irregular margins, echogenic foci, and higher TIRADS categories, were more frequently demonstrated in nodules with classic PTC and the tall cell subtype, in line with their histopathological features. Conversely, IEFV-PTC and NIFTP rarely exhibited these high-risk sonographic features. US appearance of the oncocytic subtype more frequently overlapped with IEFV-PTC, yet hypo/very hypoechoic nodules with larger nodular diameters and higher TIRADS scores may favor the diagnosis of this subtype. Conclusion: US features of certain subtypes may guide the differential diagnosis regarding shape, margin, echogenic foci, and TIRADS category of nodules; however, definitive subtyping is not yet possible using US images alone.
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Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Ultrasonografía , Organización Mundial de la Salud , Humanos , Masculino , Femenino , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/patología , Ultrasonografía/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/clasificación , Anciano , Adulto Joven , Diagnóstico Diferencial , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patologíaRESUMEN
Background: A preoperative diagnosis to distinguish malignant from benign thyroid nodules accurately and sensitively is urgently important. However, existing clinical methods cannot solve this problem satisfactorily. The aim of this study is to establish a simple, economic approach for preoperative diagnosis in eastern population. Methods: Our retrospective study included 86 patients with papillary thyroid cancer and 29 benign cases. The ITK-SNAP software was used to draw the outline of the area of interest (ROI), and Ultrosomics was used to extract radiomic features. Whole-transcriptome sequencing and bioinformatic analysis were used to identify candidate genes for thyroid nodule diagnosis. RT-qPCR was used to evaluate the expression levels of candidate genes. SVM diagnostic model was established based on the METLAB 2022 platform and LibSVM 3.2 language package. Results: The radiomic model was first established. The accuracy is 73.0%, the sensitivity is 86.1%, the specificity is 17.6%, the PPV is 81.6%, and the NPV is 23.1%. Then, CLDN10, HMGA2, and LAMB3 were finally screened for model building. All three genes showed significant differential expressions between papillary thyroid cancer and normal tissue both in our cohort and TCGA cohort. The molecular model was established based on these genetic data and partial clinical information. The accuracy is 85.9%, the sensitivity is 86.1%, the specificity is 84.6%, the PPV is 96.9%, and the NPV is 52.4%. Considering that the above two models are not very effective, We integrated and optimized the two models to construct the final diagnostic model (C-thyroid model). In the training set, the accuracy is 96.7%, the sensitivity is 100%, the specificity is 93.8%, the PPV is 93.3%, and the NPV is 100%. In the validation set, the accuracy is 97.6%, the sensitivity remains 100%, the specificity is 84.6%, the PPV is 97.3%, and the NPV is 100%. Discussion: A diagnostic panel is successfully established for eastern population through a simple, economic approach using only four genes and clinical data.
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Biomarcadores de Tumor , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/diagnóstico , Femenino , Estudios Retrospectivos , Masculino , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Adulto , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/genética , RadiómicaRESUMEN
ABSTRACT: A 23-year-old man with papillary thyroid cancer underwent radioiodine ( 131 I) treatment following total thyroidectomy and node dissection. Posttreatment 131 I SPECT/CT images revealed an additional focus of increased 131 I activity in the left adrenal gland, raising suspicion for possible adrenal metastasis. Ultimately, pathological examination confirmed the diagnosis of an adrenal cyst.
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Quistes , Radioisótopos de Yodo , Neoplasias de la Tiroides , Humanos , Masculino , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Adulto Joven , Quistes/diagnóstico por imagen , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Cáncer Papilar Tiroideo/diagnóstico por imagenRESUMEN
OBJECTIVE: This study investigates the long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating locally recurrent papillary thyroid cancer (PTC). MATERIALS AND METHODS: We retrospectively analyzed 39 consecutive patients with 61 locally recurrent PTCs (14 males, 25 females; mean ± standard deviation age, 52.8 ± 16.7 years; range 21-92 years) who underwent US-guided RFA with curative intent between September 2008 and April 2012. A subgroup of 24 patients with 37 recurrent PTCs who had a follow-up of at least 10 years were analyzed separately. All patients were followed for changes in lesion size on US and thyroglobulin (Tg) levels at 1, 3, 6, and 12 months after RFA, with follow-up every 6-12 months thereafter. Any complications were documented during the follow-up period. Recurrence-free survival (RFS) rates were assessed using Kaplan-Meier estimates. Long-term outcomes were evaluated in patients with follow-up of at least 10 years. RESULTS: The follow-up period ranged from 7 to 180 months (median 133 months). The RFS rates for the 39 patients at 3, 5, and 10 years were 86.8%, 75.5%, and 60.6%, respectively. Among the 24 patients with 37 recurrent PTCs followed for more than 10 years, the volume reduction rate was 99.9% (range 96%-100%), and the complete tumor disappearance rate was 91.9%. The mean serum Tg level also decreased significantly, from 2.66 ± 86.5 mIU/L before ablation to 0.43 ± 0.73 mIU/L (P < 0.001) at the final follow-up. In 14 (58.3%) of the 24 patients, Tg levels were undetectable (below 0.08 mIU/L) at the last follow-up. No life-threatening or delayed complications were observed during the 10-year follow-up period. CONCLUSION: The high RFS throughout the follow-up period, with efficacy and safety lasting beyond 10 years, supports US-guided RFA as a valuable option for local control of recurrent PTCs.
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Carcinoma Papilar , Recurrencia Local de Neoplasia , Ablación por Radiofrecuencia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Ultrasonografía Intervencional , Humanos , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Anciano de 80 o más Años , Ablación por Radiofrecuencia/métodos , Resultado del Tratamiento , Carcinoma Papilar/cirugía , Carcinoma Papilar/patología , Carcinoma Papilar/diagnóstico por imagen , Estudios de Seguimiento , Carcinoma/cirugía , Carcinoma/diagnóstico por imagen , Carcinoma/patologíaRESUMEN
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_shape_VoxelVolume, age, wavelet-LHL_firstorder_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_shape_VoxelVolume, original_firstorder_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.
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Enfermedad de Hashimoto , Metástasis Linfática , Aprendizaje Automático , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Ultrasonografía , Humanos , Carcinoma Papilar/diagnóstico por imagen , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Cuello/diagnóstico por imagen , Radiómica , Curva ROC , Máquina de Vectores de Soporte , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/complicaciones , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Ultrasonografía/métodosRESUMEN
PURPOSE: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown. PATIENTS AND METHODS: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC. RESULTS: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes. CONCLUSION: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis.
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Autoanticuerpos , Neoplasias de la Tiroides , Humanos , Femenino , Estudios de Casos y Controles , Masculino , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Persona de Mediana Edad , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/sangre , Adulto , Pronóstico , Estudios de Seguimiento , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/patología , Metástasis Linfática , Carcinoma Papilar/inmunología , Carcinoma Papilar/patología , Carcinoma Papilar/sangre , China/epidemiología , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/sangre , Adulto Joven , AncianoRESUMEN
Papillary thyroid carcinoma (PTC), the most common malignancy of follicular cell derivation, is generally associated with good prognosis. Nevertheless, it is important to identify patients with aggressive PTCs and unfavorable outcome. Molecular markers such as BRAFV600E mutation and TERT promoter mutations have been proposed for risk stratification. While TERT promoter mutations have been frequently associated with aggressive PTCs, the association of BRAFV600E mutation with increased recurrence and mortality is less clear and has been controversially discussed. The aim of the present study was to analyze whether differentially expressed genes can predict BRAFV600E mutations as well as TERT promoter mutations in PTCs. RNA sequencing identified a large number of differentially expressed genes between BRAFV600E and BRAFwildtype PTCs. Of those, AHNAK2, DCSTAMP, and FN1 could be confirmed in a larger cohort (n = 91) to be significantly upregulated in BRAFV600E mutant PTCs using quantitative RT-PCR. Moreover, individual PTC expression values of DCSTAMP and FN1 were able to predict the BRAFV600E mutation status with high sensitivity and specificity. The expression of TERT was detected in all PTCs harboring TERT promoter mutations and in 19% of PTCs without TERT promoter mutations. Tumors with both TERT expression and TERT promoter mutations were particularly associated with aggressive clinicopathological features and a shorter recurrence-free survival. Altogether, it will be interesting to explore the biological function of AHNAK2, DCSTAMP, and FN1 in PTC in more detail. The analysis of their expression patterns could allow the characterization of PTC subtypes and thus enabling a more individualized surgical and medical treatment.
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Mutación , Recurrencia Local de Neoplasia , Telomerasa , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Telomerasa/genética , Femenino , Masculino , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Persona de Mediana Edad , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adulto , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas de la Membrana/genética , Anciano , Transcriptoma , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Regiones Promotoras Genéticas , Proteínas del Citoesqueleto , FibronectinasRESUMEN
ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 (ACAP3) level has been confirmed to be downregulated in papillary thyroid carcinoma (PTC). Histone deacetylase inhibitors (HDACIs) have therapeutic effects on PTC. Accordingly, this study probed into the potential relation of histone deacetylase 2 (HDAC2) and ACAP3 in PTC. Expressions of ACAP3 and HDAC2 in PTC were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between HDAC2 and ACAP3 was predicted by Pearson analysis. Cell functional assays (cell counting kit-8, transwell, wound healing and flow cytometry assays) and rescue assay were carried out to determine the effects of HDAC2/ACAP3 axis on biological behaviors of PTC cells. Expressions of apoptosis-, epithelial-mesenchymal transition-, Protein Kinase B (AKT)-, and P53-related proteins were measured by Western blot. ACAP3 level was downregulated in PTC tissues and cells. ACAP3 overexpression (oe-ACAP3) suppressed viability, proliferation, migration and invasion of PTC cells, facilitated apoptosis, downregulated the expressions of Protein Kinase B (Bcl-2) and N-cadherin, upregulated the expressions of Bcl-2 associated protein X (Bax) and E-cadherin, diminished the p-AKT/AKT ratio and elevated the p-p53/p53 ratio; however, ACAP3 silencing or HDAC2 overexpression (oe-HDAC2) did the opposite. HDAC2 negatively correlated with ACAP3. The tumor-suppressing effect of oe-ACAP3 in PTC was reversed by oe-HDAC2. Collectively, ACAP3 negatively regulated by HDAC2 suppresses the proliferation and metastasis while facilitating apoptosis of PTC cells.
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Apoptosis , Proliferación Celular , Proteínas Activadoras de GTPasa , Histona Desacetilasa 2 , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Histona Desacetilasa 2/metabolismo , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/antagonistas & inhibidores , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genéticaRESUMEN
Objective:To explore the risk factors of lymph node metastasis and multiple lymph node metastasis in patients with stage CN0 papillary thyroid carcinoma. Methods:The clinical case data of 3 099 patients with CN0 papillary thyroid cancer who underwent lymph node dissection at Xijing Hospital of Air Force Medical University from January 2013 to December 2022 were retrospectively analyzed, univariate and multivariate logistic regression were used to analyze the risk factors of lymph node metastasis and multiple lymph node metastasis. Results:Male gender, age<55 years, multifocal lesions, and lesion size ≥2 cm were independent risk factors for lymph node metastasis in CN0 patientsï¼P<0.05ï¼, while diabetes was an independent protective factor for lymph node metastasisï¼P<0.05ï¼.Age<55 years, capsular invasion, and multifocal lesions were independent risk factors for the presence of ≥3 lymph nodes with metastasis ï¼P<0.05ï¼. Conclusion:In CN0 stage PTC patients, special attention should be given to the possibility of lymph node metastasis when they are male, aged <55 years, have multifocal lesions, or have lesion size >2 cm.
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Ganglios Linfáticos , Metástasis Linfática , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Masculino , Neoplasias de la Tiroides/patología , Femenino , Persona de Mediana Edad , Cáncer Papilar Tiroideo/patología , Factores de Riesgo , Estudios Retrospectivos , Ganglios Linfáticos/patología , Carcinoma Papilar/patología , Estadificación de Neoplasias , Adulto , Modelos Logísticos , Escisión del Ganglio LinfáticoRESUMEN
Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents.
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Proliferación Celular , Pulpa Dental , Vesículas Extracelulares , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Pulpa Dental/citología , Vesículas Extracelulares/metabolismo , Cáncer Papilar Tiroideo/terapia , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Línea Celular Tumoral , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Vía de Señalización Wnt , Medios de Cultivo Condicionados/farmacologíaRESUMEN
This study aimed to investigate the expression of microRNAs (miRNAs) -146b-3p, -221-5p, -222-3p, and -21a-3p and the methylation pattern of the thyroid-stimulating hormone receptor (TSHR) gene in blood plasma samples from papillary thyroid cancer (PTC) patients before and after thyroidectomy compared to healthy controls (HCs). This study included 103 participants, 46 PTC patients and 57 HCs, matched for gender and age. Significantly higher preoperative expression levels of miRNAs and TSHR methylation were determined in the PTC patients compared to HCs. Post-surgery, there was a notable decrease in these biomarkers. Elevated TSHR methylation was linked to larger tumor sizes and lymphovascular invasion, while increased miRNA-222-3p levels correlated with multifocality. Receiver operating characteristic (ROC) analysis showed AUCs below 0.8 for all candidate biomarkers. However, significant changes in the expression of all analyzed miRNAs and TSHR methylation levels indicate their potential to differentiate PTC patients from healthy individuals. These findings suggest that miRNAs and TSHR methylation levels may serve as candidate biomarkers for early diagnosis and monitoring of PTC, with the potential to distinguish PTC patients from healthy individuals. Further research is needed to validate these biomarkers for clinical application.
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Biomarcadores de Tumor , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , MicroARNs , Receptores de Tirotropina , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , MicroARNs/sangre , MicroARNs/genética , Femenino , Masculino , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/sangre , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Persona de Mediana Edad , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Adulto , Receptores de Tirotropina/genética , Estudios de Casos y Controles , Curva ROCRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). MATERIALS AND METHODS: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates. In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. RESULTS: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0-40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%-86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%-19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%-11.4%), 26.8% (95% CI: 2.7%-44.9%), and 51.2% (95% CI: 0%-79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). CONCLUSION: Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.
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Microondas , Ablación por Radiofrecuencia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Estudios Retrospectivos , Adulto , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Microondas/uso terapéutico , Ablación por Radiofrecuencia/métodos , Resultado del Tratamiento , Persona de Mediana Edad , Progresión de la Enfermedad , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. METHODS: The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. RESULTS: In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. CONCLUSION: Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.