RESUMEN

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Asunto(s)

Clorofilidas , Indoles , Platino (Metal) , Polímeros , Porfirinas , Neoplasias de la Tiroides , Microambiente Tumoral , Terapia por Ultrasonido , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/metabolismo , Humanos , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Indoles/química , Terapia por Ultrasonido/métodos , Porfirinas/química , Porfirinas/farmacología , Polímeros/química , Animales , Platino (Metal)/química , Platino (Metal)/uso terapéutico , Platino (Metal)/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Apoptosis/efectos de los fármacos , Nanopartículas/química , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Quinolinas/farmacología , Quinolinas/química , Ratones Desnudos , Portadores de Fármacos/química

RESUMEN

To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.

Asunto(s)

Yodo , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biología Computacional/métodos , Femenino , Masculino , Aprendizaje Automático , Persona de Mediana Edad , Glándula Tiroides/patología , Glándula Tiroides/metabolismo , Curva ROC , Diferenciación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo

RESUMEN

OBJECTIVE: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms. METHODS: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated. RESULTS: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively. CONCLUSIONS: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

Asunto(s)

Microondas , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Microondas/uso terapéutico , Estudios Retrospectivos , Adenocarcinoma Folicular/cirugía , Adenocarcinoma Folicular/patología , Resultado del Tratamiento , Técnicas de Ablación/métodos , Técnicas de Ablación/efectos adversos , Anciano

RESUMEN

PURPOSE: The management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis. METHODS: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %. CONCLUSION: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient's age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.

Asunto(s)

Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología , Nódulo Tiroideo/diagnóstico , Femenino , Persona de Mediana Edad , Masculino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto , Análisis Mutacional de ADN/métodos , Anciano , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Biomarcadores de Tumor/genética , Sensibilidad y Especificidad , Biopsia con Aguja Fina , Citología

RESUMEN

Objective: To describe cytologic findings from mandibular and superficial cervical lymph nodes in dogs with thyroid carcinoma and to determine prognostic factors associated with lymph node metastasis. Animals: A total of 71 client-owned dogs with confirmed thyroid carcinoma that had cytologic results from at least 1 mandibular or superficial cervical lymph node between 2010 and 2020. Procedure: Medical records from 2 referral veterinary hospitals were retrospectively reviewed. Cytology of lymph nodes was reviewed for presence of metastasis by diplomates of the American College of Veterinary Pathologists. Thyroid tumor diameter and volume, tumor fixation, bilateral location, vascular invasion, and stage were recorded to determine effects on nodal metastasis. Results: A total of 154 lymph nodes (104 mandibular and 50 superficial cervical lymph nodes) from 71 dogs were cytologically evaluated, and 1/154 (0.6%) and 2/154 (1.3%) lymph nodes were noted to be definitively metastatic or probably metastatic, respectively. Given the infrequent rate of nodal metastasis (1.9% or less), statistical analysis of potential prognostic variables was not completed. Conclusion and clinical relevance: Routine lymph node cytology of mandibular and superficial cervical lymph nodes appeared to be of low yield when assessing for metastasis of canine thyroid carcinomas. The medial retropharyngeal and deep cervical lymph nodes should continue to be evaluated as they appeared to have higher metastatic rates, based on historic reports. Additional studies are needed to determine prognostic factors associated with lymph node metastasis and effects on patient survival.

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Résultats cytologiques dans les ganglions lymphatiques cervicaux mandibulaires et superficiels de chiens atteints d'un carcinome thyroïdien. Objectif: Décrire les résultats cytologiques obtenus des ganglions lymphatiques mandibulaires et cervicaux superficiels chez des chiens atteints d'un carcinome thyroïdien et déterminer les facteurs pronostiques associés aux métastases ganglionnaires. Animaux: Un total de 71 chiens appartenant à des clients atteints d'un carcinome thyroïdien confirmé avec des résultats cytologiques d'au moins un ganglion lymphatique cervical mandibulaire ou superficiel entre 2010 et 2020. Procédure: Les dossiers médicaux de 2 hôpitaux vétérinaires de référence ont été examinés rétrospectivement. La cytologie des ganglions lymphatiques a été examinée pour détecter la présence de métastases par des diplomates de l'American College of Veterinary Pathologists. Le diamètre et le volume de la tumeur thyroïdienne, la fixation de la tumeur, la localisation bilatérale, l'invasion vasculaire et le stade ont été notés pour déterminer les effets sur les métastases ganglionnaires. Résultats: Au total, 154 ganglions lymphatiques (104 ganglions lymphatiques mandibulaires et 50 ganglions lymphatiques cervicaux superficiels) provenant de 71 chiens ont été évalués par cytologie, et 1/154 (0,6 %) et 2/154 (1,3 %) ganglions lymphatiques ont été notés comme définitivement métastatiques ou probablement métastatiques, respectivement. Compte tenu du taux peu fréquent de métastases ganglionnaires (1,9 % ou moins), l'analyse statistique des variables pronostiques potentielles n'a pas été complétée. Conclusion et pertinence clinique: La cytologie de routine des ganglions lymphatiques mandibulaires et cervicaux superficiels semblait être de faible rendement lors de l'évaluation des possibilités de métastases des carcinomes thyroïdiens canins. Les ganglions lymphatiques rétropharyngés médiaux et cervicaux profonds doivent continuer à être évalués car ils semblent présenter des taux métastatiques plus élevés, sur la base des rapports historiques. Des études supplémentaires sont nécessaires pour déterminer les facteurs pronostiques associés aux métastases ganglionnaires et les effets sur la survie des patients.(Traduit par Dr Serge Messier).

Asunto(s)

Enfermedades de los Perros , Ganglios Linfáticos , Metástasis Linfática , Neoplasias de la Tiroides , Animales , Perros , Neoplasias de la Tiroides/veterinaria , Neoplasias de la Tiroides/patología , Enfermedades de los Perros/patología , Ganglios Linfáticos/patología , Estudios Retrospectivos , Metástasis Linfática/patología , Masculino , Femenino , Cuello/patología , Mandíbula/patología

RESUMEN

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.

Asunto(s)

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 Joven

RESUMEN

Introduction: The prevalence of thyroid nodules and malignancies in the elderly is a growing concern. Thyroid nodules in this population have unique characteristics, requiring careful treatment strategies that balance risks and benefits. Oncocytic carcinoma of the thyroid (OCA) is a rare, aggressive subtype with diagnostic challenges. Methods: This case features an 84-year-old patient who presented with a neck mass and symptoms of asphyxia. Clinical evaluation, imaging studies, and biopsy were conducted to assess the nature of the thyroid lesion. Molecular testing, including genetic analysis, was performed to identify specific mutations associated with OCA and guide treatment decisions. Results: The patient was diagnosed with oncocytic carcinoma of the thyroid. The molecular testing revealed specific genetic mutations indicative of OCA, confirming the diagnosis. The presence of these mutations guided the treatment plan, emphasizing the importance of molecular diagnostics in managing thyroid malignancies, especially in the elderly. Discussion: This case illustrates the complexities of diagnosing and treating thyroid malignancies in the elderly. Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention.

Asunto(s)

Asfixia , Mutación , Regiones Promotoras Genéticas , Telomerasa , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Anciano de 80 o más Años , Telomerasa/genética , Regiones Promotoras Genéticas/genética , Asfixia/genética , Adenoma Oxifílico/genética , Adenoma Oxifílico/patología , Adenoma Oxifílico/diagnóstico , Femenino , Masculino

RESUMEN

Background: The necessity and therapeutic value of lymph node dissection (LND) in early stage T1 MTC patients remain controversial. Methods: Patients with T1MTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Poisson regression analysis was utilized to investigate promotive factors for lymph node metastasis in T1MTC patients. Fisher's exact test was employed to calculate baseline differences between non-LND and LND groups. Propensity score match (PSM) was used to control baseline bias. Survival outcomes were calculated by Kaplan-Meier method and log-rank test. Multivariable Cox regression assessed the prognostic impact of LND across subgroups. Results: Of 3298 MTC cases, 50.4% were T1MTC. The lymph node metastasis rate increased along with the T stage (from 22.2% to 90.5%). Among 1231 T1MTC patients included after exclusion criteria, 72.0% underwent LND and 22.0% had lymph node metastasis. Patients aged younger than 44 years (RR=1.700, p<0.001), male (RR=1.832, p<0.001), and with tumor larger than 10mm (RR=2.361, p<0.001) were more likely to have lymph node metastasis, while elderly patients (p<0.001) and those with microcarcinoma (p<0.001) were more likely to undergo non-LND procedures. LND provided no OS or DSS benefit over non-LND before and after propensity score match (matched 10-year OS/DSS: LND 83.8/96.2% vs non-LND 81.9/99.3%, p>0.05). Subgroup analyses revealed no prognostic gain with LND in any subgroup (p>0.05). Conclusion: Nearly half of MTC patients were diagnosed at T1 stage and had low lymph node risk. Different from ATA guidelines, avoiding routine LND conferred similar prognosis to standard procedures while potentially improving quality of life. Large-scale prospective multi-center studies should be conducted to further validate these findings.

Asunto(s)

Escisión del Ganglio Linfático , Metástasis Linfática , Programa de VERF , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Masculino , Femenino , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/mortalidad , Adulto , Persona de Mediana Edad , Estudios de Cohortes , Pronóstico , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/mortalidad , Estadificación de Neoplasias , Anciano , Adulto Joven

RESUMEN

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.

Asunto(s)

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 Preoperatorio

RESUMEN

OBJECTIVE: This study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC). METHODS: This prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis. RESULTS: Serum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC. CONCLUSION: Serum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC.

Asunto(s)

Adenocarcinoma Folicular , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Biomarcadores de Tumor , Proteína 1 Similar a Quitinasa-3 , Subunidad alfa del Factor 1 Inducible por Hipoxia , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Humanos , Proteína 1 Similar a Quitinasa-3/sangre , Femenino , Masculino , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Persona de Mediana Edad , Pronóstico , Adulto , Adenocarcinoma Folicular/sangre , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/mortalidad , Estudios Prospectivos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/mortalidad , Anciano , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Ensayo de Inmunoadsorción Enzimática , Valores de Referencia , Adulto Joven , Estadísticas no Paramétricas , Curva ROC

RESUMEN

Objectives: This study aimed to evaluate the effectiveness of thyroid fine needle aspiration cytology (FNAC) using a novel-cell preserving matrix called Cytomatrix in improving diagnostic accuracy for thyroid nodules. Materials and methods: Fifty patients undergoing thyroidectomy were enrolled and FNAC was performed on the excised thyroid glands, with the collected sample being placed on the Cytomatrix. The results were compared with histopathological analysis, and diagnostic performance was assessed statistically. Results: Cytomatrix demonstrated an accuracy of 96%, sensitivity of 84.61%, and specificity of 100%. Concordance between cytological and histopathological findings highlighted Cytomatrix's potential to enhance thyroid FNAC accuracy. Conclusion: FNAC using Cytomatrix shows promise in improving diagnostic accuracy for thyroid nodules. Its application, marked by faster processing and efficient resource utilization, coupled with the preservation of cellular architecture, holds considerable potential in enhancing cytological diagnosis, thus optimizing patient management strategies.

Asunto(s)

Nódulo Tiroideo , Humanos , Nódulo Tiroideo/patología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/cirugía , Biopsia con Aguja Fina/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Tiroidectomía/métodos , Citodiagnóstico/métodos , Anciano , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Sensibilidad y Especificidad , Adulto Joven , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/cirugía , Citología

RESUMEN

Objectives: Thyroid cancer (THCA) is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide. And the number of patients dying from THCA has also gradually risen because the incidence continues to increase, so the mechanisms related to effective targets is necessary to improve the survival. This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer (THCA) cell proliferation and the associated pathways. Methods: Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development. COL4A2 expression in THCA tissues was analyzed using immunohistochemistry, and survival information was determined via Kaplan‒Meier curves. The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses. Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity, respectively. Downstream of COL4A2 was identified by Gene set enrichment analysis (GSEA). The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model. Results: Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2. THCA patients with high COL4A2 expression had shorter recurrence-free survival. Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity. The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines. The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival. Conclusions: COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

Asunto(s)

Proliferación Celular , Colágeno Tipo IV , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Neoplasias de la Tiroides , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Ratones , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Colágeno Tipo IV/metabolismo , Colágeno Tipo IV/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Biología Computacional/métodos , Ensayos Antitumor por Modelo de Xenoinjerto , Pronóstico

RESUMEN

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.

Asunto(s)

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/metabolismo

RESUMEN

Thyroid cancer is the most frequently observed endocrine-related malignancy among which anaplastic thyroid cancer (ATC) is the most fatal subtype. The synthesis of protein is active to satisfy the rapid growth of ATC tumor, but the mechanisms regulating protein synthesis are still unknown. Our research revealed that kinetochore protein NUF2 played an essential role in protein synthesis and drove the progression of ATC. The prognosis of patients with thyroid carcinoma was positively correlated with high NUF2 expression. Depletion of NUF2 in ATC cells notably inhibited the proliferation and induced apoptosis, while overexpression of NUF2 facilitated ATC cell viability and colony formation. Deletion of NUF2 significantly suppressed the growth and metastasis of ATC in vivo. Notably, knockdown of NUF2 epigenetically inhibited the expression of magnesium transporters through reducing the abundance of H3K4me3 at promoters, thereby reduced intracellular Mg2+ concentration. Furthermore, we found the deletion of NUF2 or magnesium transporters significantly inhibited the protein synthesis mediated by the PI3K/Akt/mTOR pathway. In conclusion, NUF2 functions as an emerging regulator for protein synthesis by maintaining the homeostasis of intracellular Mg2+, which finally drives ATC progression.

Asunto(s)

Progresión de la Enfermedad , Homeostasis , Magnesio , Carcinoma Anaplásico de Tiroides , Animales , Femenino , Humanos , Ratones , Apoptosis , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Magnesio/metabolismo , Ratones Desnudos , Biosíntesis de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Serina-Treonina Quinasas TOR/metabolismo

RESUMEN

Our research seeks to evaluate the utility of intraoperative frozen analysis of sentinel lymph nodes (SLNs) in the lateral cervical compartment (LCC) as a tool to inform decision-making regarding therapeutic neck dissection in patients with medullary thyroid carcinoma (MTC). This is particularly relevant due to the variability observed in guidelines regarding the indication for lateral neck dissection in this patient population. The study comprised 64 patients (25 males, 39 females) aged between 29 and 81 years, with a median age of 59, who underwent surgery for MTC at stage T1-3N0-1M0 between January 1, 2012, and December 31, 2020. A standardized surgical approach involving total thyroidectomy with central neck dissection was adopted. LCC dissection was reserved for patients with clinically apparent nodal metastases. In patients lacking clinical evidence of nodal involvement, SLNs were identified using patent blue dye, excised, and subjected to intraoperative frozen analysis. If metastasis was confirmed, LCC dissection was subsequently performed. Among the study participants, 14 individuals (21.9%) underwent therapeutic LCC dissection due to clinical lymph node (LN) metastases. This intervention resulted in clinical remission for 9 patients, while disease progression was observed in 5 cases, leading to 2 fatalities. In the remaining cohort of 50 patients clinically negative for nodal involvement, SLNs were successfully identified and examined in 38 cases, revealing metastases in 6 patients (15.8%). Among both subsets of patients with analyzed SLNs, irrespective of metastatic status, one patient each required repeat surgery due to disease recurrence; however, all patients eventually achieved clinical remission. Lymphatic mapping in the LCC plays a pivotal role in detecting early metastases, thereby aiding in the avoidance of unnecessary repeat neck surgeries, and ultimately improving the prognosis in patients with MTC.

Asunto(s)

Carcinoma Neuroendocrino , Disección del Cuello , Ganglio Linfático Centinela , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Disección del Cuello/métodos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Adulto , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Anciano de 80 o más Años , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Metástasis Linfática , Tiroidectomía/métodos , Biopsia del Ganglio Linfático Centinela/métodos

RESUMEN

Recent insights into the mechanisms controlling gene expression identified enhancer-associated long non-coding RNAs (elncRNAs) as master players of transcription in cancers. RUNX2, a mammalian RUNT-related transcription factor, is increasingly recognized in cancer biology for its role in supporting survival and progression also in thyroid cancer (TC). We recently identified, within the RUNX2 locus, a novel elncRNA that we named RAIN (RUNX2 associated intergenic lncRNA). We showed that RAIN and RUNX2 expression correlate in TC, both in vitro and in vivo, and that RAIN promotes RUNX2 expression by interacting with and affecting the activity of the RUNX2 P2 promoter through two distinct mechanisms. Here, we took forward these observations to explore the genome-wide transcriptional function of RAIN and its contribution to the RUNX2-dependent gene expression program in TC. By combining multiple omics data, we demonstrated that RAIN functionally cooperates with RUNX2 to the regulation of a subset of functionally related genes involved in promoting matrix remodeling, migration, and loss of differentiation. We showed that RAIN interacts with RUNX2 and its expression is required for the efficient recruitment of this TF to its target regulatory regions. In addition, our data revealed that besides RUNX2, RAIN governs a hierarchically organized complex transcriptional program by controlling a core of cancer-associated TFs that, in turn, orchestrate the expression of downstream genes. This evidence indicates that the functional cooperation observed between RAIN and RUNX2 can be a diffuse work mechanism for this elncRNA.

Asunto(s)

Subunidad alfa 1 del Factor de Unión al Sitio Principal , ARN Largo no Codificante , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transcripción Genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Regiones Promotoras Genéticas/genética

RESUMEN

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.

Asunto(s)

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 Genes

Asunto(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 Edad

RESUMEN

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer, and it has a poor prognosis and high probability of metastatic recurrence. The long-term survival of cancer cells depends on their ability to settle in a favorable environment. Cancer cells interact with other cells in the tumor microenvironment to shape the "soil" and make it suitable for cell growth by forming an extremely complex tumor ecosystem. The extracellular matrix (ECM) is an essential component of the tumor ecosystem, and its biological and mechanical changes strongly affect tumor invasion, metastasis, immune escape and drug resistance. Compared to normal tissues, biological processes, such as collagen synthesis and ECM signaling, are significantly activated in ATC tissues. However, how ATC triggers changes in the properties of the ECM and its interaction with the ECM remain poorly characterized. Therefore, an in-depth study of the regulatory mechanism of the abnormal activation of ECM signaling in ATC is highly important for achieving the therapeutic goal of exerting antitumor effects by destroying the "soil" in which cancer cells depend for survival. In this research, we revealed the aberrant activation state of ECM signaling in ATC progression and attempted to uncover the potential mechanism of action of ECM components in ATC, with the aim of providing new drug targets for ATC therapy.

Asunto(s)

Matriz Extracelular , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Microambiente Tumoral , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/metabolismo , Humanos , Matriz Extracelular/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/metabolismo , Transducción de Señal

RESUMEN

PURPOSE: The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer. MATERIAL AND METHODS: The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with "focal thyroid uptake" on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed. RESULTS: Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included "focal thyroid uptake." About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3). CONCLUSION: In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET.

Asunto(s)

Radioisótopos de Carbono , Colina , Hallazgos Incidentales , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Nódulo Tiroideo , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Masculino , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Colina/farmacocinética , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Ultrasonografía/métodos , Anciano de 80 o más Años , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patología , Radiofármacos/farmacocinética