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1.
BMC Genomics ; 22(1): 576, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315405

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. METHODS: The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. RESULTS: We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. CONCLUSIONS: Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.


Assuntos
Carcinoma Papilar , Ferroptose , Neoplasias da Glândula Tireoide , Biomarcadores Tumorais , Carcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia , Prognóstico , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Microambiente Tumoral
2.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204950

RESUMO

The dysregulation of autophagy is important in the development of many cancers, including thyroid cancer, where V600EBRAF is a main oncogene. Here, we analyse the effect of V600EBRAF inhibition on autophagy, the mechanisms involved in this regulation and the role of autophagy in cell survival of thyroid cancer cells. We reveal that the inhibition of V600EBRAF activity with its specific inhibitor PLX4720 or the depletion of its expression by siRNA induces autophagy in thyroid tumour cells. We show that V600EBRAF downregulation increases LKB1-AMPK signalling and decreases mTOR activity through a MEK/ERK-dependent mechanism. Moreover, we demonstrate that PLX4720 activates ULK1 and increases autophagy through the activation of the AMPK-ULK1 pathway, but not by the inhibition of mTOR. In addition, we find that autophagy blockade decreases cell viability and sensitize thyroid cancer cells to V600EBRAF inhibition by PLX4720 treatment. Finally, we generate a thyroid xenograft model to demonstrate that autophagy inhibition synergistically enhances the anti-proliferative and pro-apoptotic effects of V600EBRAF inhibition in vivo. Collectively, we uncover a new role of AMPK in mediating the induction of cytoprotective autophagy by V600EBRAF inhibition. In addition, these data establish a rationale for designing an integrated therapy targeting V600EBRAF and the LKB1-AMPK-ULK1-autophagy axis for the treatment of V600EBRAF-positive thyroid tumours.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Apoptose/efeitos dos fármacos , Autofagia/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis/farmacologia , Mutação/genética , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
3.
Zhonghua Zhong Liu Za Zhi ; 43(6): 629-634, 2021 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-34289553

RESUMO

Thyroid cancer is the most common endocrine malignancy, and thyroid carcinoma (PTC) has the highest incidence rate, accounts for about 85%~90% of thyroid carcinoma. There are many markers of PTC, such as murine sarcoma viral oncogene homolog B1 (BRAF), telomerase reverse transcriptase, Ki-67, microRNA-146b, PDZ and LIM domain 5 (PDLIM5). Among them, BRAF plays an important role in the carcinogenesis, development and prognosis of PTC. This article summarizes the research progress of BRAF signaling pathway, its role in the carcinogenesis, development and prognosis of PTC, its clinical correlation with the clinical pathological characteristics of PTC, and its application in the diagnosis and treatment of PTC to provide the references to readers.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Animais , Carcinoma Papilar/diagnóstico , Humanos , Camundongos , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética
4.
World J Surg Oncol ; 19(1): 211, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256769

RESUMO

OBJECTIVE: The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). METHODS: A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. RESULTS: The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. CONCLUSION: The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Adulto , China/epidemiologia , Humanos , Metástase Linfática , Masculino , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética
5.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199867

RESUMO

NIS is a potent iodide transporter encoded by the SLC5A5 gene. Its expression is reduced in papillary thyroid carcinoma (PTC). In this study we analyzed the impact of miR-181a-5p on NIS expression in the context of PTC. We used real-time PCR to analyze the expression of SLC5A5 and miR-181a-5p in 49 PTC/normal tissue pairs. Luciferase assays and mutagenesis were performed to confirm direct binding of miR-181a-5p to the 3'UTR of SLC5A5 and identify the binding site. The impact of modulation of miR-181a-5p using appropriate plasmids on endogenous NIS and radioactive iodine accumulation was verified. We confirmed downregulation of SLC5A5 and concomitant upregulation of miR-181a-5p in PTC. Broadly used algorithms did not predict the binding site of miR-181a-5p in 3'UTR of SLC5A5, but we identified and confirmed the binding site through mutagenesis using luciferase assays. In MCF7 and HEK293-flhNIS cell lines, transfection with mir-181a-expressing plasmid decreased endogenous SLC5A5, whereas silencing of miR-181a-5p increased it. We observed similar tendencies in protein expression and radioactive iodine accumulation. This study shows for the first time that miR-181a-5p directly regulates SLC5A5 expression in the context of PTC and may decrease efficacy of radioiodine treatment. Accordingly, miR-181a-5p may serve as an emerging target to enhance the efficacy of radioactive iodine therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Simportadores/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Simportadores/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
6.
Medicine (Baltimore) ; 100(25): e26388, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160418

RESUMO

ABSTRACT: Radioiodine-refractory thyroid cancers (IRTCs) are uncommon and have a poor prognosis. Treatment options for radioiodine-refractory and anaplastic tumors (ATCs) are limited. Although the genomic landscape of thyroid cancer has been studied, there is little evidence on whether next-generation sequencing (NGS) findings translate to tumor control.We analyzed all patients with IRTC and ATC who underwent commercially available NGS in 3 cancer centers.Twenty-two patients were identified, 16 patients with IRTCs and 6 patients with ATCs. Eighteen (82%) had targetable findings in NGS, nine patients were treated accordingly. Median progression-free survival for targeted treatment was 50 months [95% confidence interval (CI95%) 9.8-66.6] and2 months (CI95% 0.2-16.5) for IRTC and ATC, respectively. Of 4 patients who achieved durable responses of 7 to 50 months, 2 are ongoing. The estimated median OS of IRTC receiving targeted treatment was not reached (CI95% 89.7-111.4 months) and was 77.8 months (CI95% 52.5-114.6) for patients treated conventionally (P = .3).NGS may detect clinically significant genetic alterations and benefit patients with advanced thyroid cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/terapia , Neoplasias da Glândula Tireoide/terapia , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Radioisótopos do Iodo/farmacologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/genética , Estudos Retrospectivos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/mortalidade
7.
J Biol Regul Homeost Agents ; 35(3): 909-920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34155880

RESUMO

Papillary thyroid cancer (PTC) is currently one of the most common endocrine tumors worldwide. Long non-coding RNA (LncRNA) is a vital regulator in the biological processes of diverse tumors. Hence, this work aimed to clarify the role and mechanism of lncRNA OIP5-AS1 in PTC progression. OIP5-AS1 and miR-429 expression levels in PTC tissues and cells were examined using qRT-PCR. Immunohistochemical staining (IHC) was applied to detect X-linked inhibitors of apoptosis protein (XIAP) expression in PTC tissues. A dual-luciferase reporter gene experiment was employed to validate the relationship for miR-429 and XIAP, miR-429 and OIP5-AS1. The regulatory effects of OIP5-AS1 on PTC cell proliferation, migration, and invasion was detected using the MTT, BrdU, Transwell and Western blot assays. In this work we reported that OIP5-AS1 expression was up-modulated in PTC tissues and cell lines. OIP5-AS1 overexpression enhanced the proliferation and metastasis of PTC cells, but the transfection of miR-429 mimics reversed the functions of OIP5-AS1 on the proliferation, migration, and invasion of PTC cells. Additionally, OIP5-AS1 was identified as a competitive endogenous RNA (ceRNA) that repressed miR-429, thereby increasing the expression level of XIAP. Taken together, the findings confirm that OIP5-AS1 accelerates PTC progression via modulating the miR-429/XIAP axis and imply that OIP5-AS1 is likely to be a therapeutic target for PTC.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
8.
BMJ Case Rep ; 14(6)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127502

RESUMO

Struma ovarii (SO) is a rare ovarian teratoma containing abundant mature thyroid tissue. Malignant transformation is even less common and distant metastasis is documented in about 5%-10%. The time from diagnosis of primary SO to metastatic disease varies. As malignant SO is rare, there are no uniform diagnostic criteria or treatment guidelines. Management is usually extrapolated from that of thyroid malignancy. We report a patient who relapsed 12 years from the initial diagnosis and metastasised to the lungs 5 years after the first recurrence. Our patient was treated with total thyroidectomy followed by radioactive iodine, and retreated on progression in the lungs. The tumour harboured high microsatellite instability and treatment with programmed cell death protein 1 inhibitor was initiated. This case shows the long latency of SO with the rare phenomenon of metastasis. It also highlights the importance of molecular testing for rare cancers such as this.


Assuntos
Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Instabilidade de Microssatélites , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Estruma Ovariano/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia
9.
Aging (Albany NY) ; 13(12): 16500-16512, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34153004

RESUMO

Circular RNAs (circRNAs) are one type of non-coding RNA. They act as important role in regulating various biological processes in the malignant progression. But we don't clearly know the specific mechanism of the majority circRNAs in papillary thyroid tumor progression. In the current study, we explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown of circKIF4A could suppress papillary thyroid cell growth and migration. In addition, RIP assays and dual luciferase vector reporter assays were further conducted. Our consequence showed circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. In conclusion, our study proved that circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future.


Assuntos
Progressão da Doença , Ferroptose/genética , MicroRNAs/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , RNA Circular/metabolismo , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Regulação para Cima/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , MicroRNAs/genética , Metástase Neoplásica , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , RNA Circular/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(1): 90-96, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-34117845

RESUMO

To investigate the expression of xenotropic and polytropic retrovirus receptor 1 () in papillary thyroid cancer (PTC) and its clinical implication. The HPA and UALCAN databases were used to explore the expression of XPR1 in PTC and normal tissues. The cBioPortal database was used to obtain the clinical data of PTC patients and gene expression profile. The correlation of expression with gender,age,sub-types,T stage,N stage,M stage and clinical stage of patients were analyzed. Cox regression was conducted to analysis the factors affecting the prognosis of PTC patients. The mutation of was assessed through cBioPortal database. GO and KEGG analyses were used to explore the related biological pathway of involved in PTC. HPA database analysis showed that XPR1 was highly expressed in PTC tissue compared with normal tissues. UALCAN analysis displayed that expression was significantly higher in PTC tissue compared with normal tissues (<0.01),and the highest and lowest expressions of were observed in tall cell and follicular sub-type of PTC,respectively. The expression of was correlated with age,sub-types,T stage,N stage and disease stage of PTC patients (<0.05 or <0.01),but was not correlated with gender and M stage (all >0.05). Cox regression analysis showed that was an independent prognostic factor of PTC patients (=2.894,<0.05). The cBioPortal database indicated that the mutation appeared in 6% PTC patients; the mutation type mainly was missense and the mutation point was located at the E615K. Enrichment analysis indicated that might affect the PTC progression through involvement in metabolic pathway. is highly expressed in PTC tissues,which is associated with the prognosis of patients. Metabolic pathway associated with might play an important role in PTC progression,indicating that might be a novel biomarker for diagnosis and treatment of PTC.


Assuntos
Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Prognóstico , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
11.
Croat Med J ; 62(2): 110-119, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33938650

RESUMO

AIM: To determine the frequency and type of RET mutation in Slovenian medullary thyroid cancer (MTC) patients and estimate the crude annual incidence of MTC in Slovenia. METHODS: This referral-center retrospective analysis involved 186 MTC patients diagnosed between 1995 and 2015 and their relatives who underwent genetic counseling and testing. The crude incidence rate of MTC was estimated with the joinpoint regression analysis. Genomic DNA was isolated, and exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene were amplified with polymerase chain reaction. Point mutations of the RET gene were detected by single-strand conformation analysis and DNA sequencing. Detected mutations were confirmed by restriction enzymes. RESULTS: The average crude annual incidence rate of MTC in Slovenia was 0.34/100,000. A germline mutation in the RET proto-oncogene was identified in 25.9% of MTC patients. The most frequently altered codons were codons 634 and 618, followed by codon 790, codon 804, and codon 918. CONCLUSIONS: Annual incidence increase and nation-specific frequency of RET mutations justify the future use of genetic counseling and testing of MTC patients in Slovenia.


Assuntos
Neoplasia Endócrina Múltipla Tipo 2a , Neoplasias da Glândula Tireoide , Carcinoma Neuroendócrino , Mutação em Linhagem Germinativa , Humanos , Incidência , Mutação , Taxa de Mutação , Proteínas Proto-Oncogênicas c-ret/genética , Estudos Retrospectivos , Eslovênia/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(4): 549-554, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33963714

RESUMO

OBJECTIVE: To explore the role of CTHRC1 in regulating the proliferation and apoptosis of papillary thyroid cancer cells. OBJECTIVE: Papillary thyroid cancer TPC-1 cells were transfected with a small interfering RNA (siRNA) targeting CTHRC1, with the cells transfected with a scrambled sequence as the negative control. The changes in cell proliferation and apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry with AV/PI double staining, respectively. The expression of c-caspase-3, c-PARP1 and phosphorylation of ERK1/2 in the cells were examined with Western blotting. OBJECTIVE: Transfection with the siRNA sequence significantly decreased the mRNA and protein levels of CTHRC1 in TCP-1 cells (P < 0.05). Compared with blank and negative control cells, TCP-1 cells with RNA interference of CTHRC1 showed significantly lowered proliferative activity and enhanced cell apoptosis (P < 0.05) with significantly increased expressions of c-caspase-3 and c-PARP1 and phosphorylation of ERK1/2 (P < 0.05). OBJECTIVE: RNA interference of CTHRC1 promotes the proliferation and inhibits apoptosis of papillary thyroid cancer cells possibly by activating the ERK1/2 pathway.


Assuntos
Apoptose , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Proliferação de Células , Proteínas da Matriz Extracelular/metabolismo , Humanos , Interferência de RNA , RNA Interferente Pequeno/genética , Neoplasias da Glândula Tireoide/genética , Transfecção
13.
Arch Endocrinol Metab ; 64(6): 751-757, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34033285

RESUMO

Objective: Although the prognostic role of BRAFV600E mutation in papillary thyroid carcinoma (PTC) is controversial, the American Thyroid Association (ATA) includes the mutational status in their risk stratification system. To evaluate the impact of the BRAFV600E mutation status on PTC risk stratification. Methods: PTC patients attending a university-based hospital who had the analysis of the BRAFV600E mutation were included. Persistent disease was defined as the presence of biochemical or structural disease. The performance of the ATA risk stratification system on predicting persistent disease with or without the BRAFV600E mutation status information was evaluated. Results: Of the 134 patients evaluated, 44 (32.8%) carried BRAFV600E mutation. The median tumor size was 1.7 cm (P25-75 1.0-3.0), 64 (47.8%) patients had lymph node, and 11 (8.2%) distant metastases. According to the ATA risk stratification system, patients were classified as low, intermediate, and high risk in 55 (41%), 59 (44%), and 20 (14%) patients, respectively. The data on BRAFV600E mutation reclassified 12 (8.9%) patients from low to intermediate risk. After a median follow-up of 8.5 years, the prevalence of persistent disease was similar in patients with and without BRAFV600E mutation (P = 0.42). Multivariate analysis failed to demonstrate an association between the BRAFV600E mutation and persistent disease status (RR 0.96; 95%CI 0.47-1.94). Notably, none of the patients reclassified from low to intermediate risk showed persistent disease on follow-up. Conclusion: Inclusion of BRAFV600E mutational status has a limited impact on risk stratification and does not add to the prediction of outcomes in PTC patients.


Assuntos
Carcinoma Papilar , Carcinoma , Neoplasias da Glândula Tireoide , Carcinoma/genética , Carcinoma Papilar/genética , Humanos , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Medição de Risco , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
14.
Arch Endocrinol Metab ; 64(5): 630-635, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34033305

RESUMO

Objective: Follicular lesions of the thyroid with papillary carcinoma nuclear characteristics are classified as infiltrative follicular variant of papillary thyroid carcinoma-FVPTC (IFVPTC), encapsulated/well demarcated FVPTC with tumour capsular invasion (IEFVPTC), and the newly described category "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) formerly known as non-invasive encapsulated FVPTC. This study evaluated whether computerized image analysis can detect nuclear differences between these three tumour subtypes. Methods: Slides with histological material from 15 cases of NIFTP and 33 cases of FVPTC subtypes (22 IEFVPTC, and 11 IFVPTC) were analyzed using the Image J image processing program. Tumour cells were compared for both nuclear morphometry and chromatin textural characteristics. Results: Nuclei from NIFTP and IFVPTC tumours differed in terms of chromatin textural features (grey intensity): mean (92.37 ± 21.01 vs 72.99 ± 14.73, p = 0.02), median (84.93 ± 21.17 vs 65.18 ± 17.08, p = 0.02), standard deviation (47.77 ± 9.55 vs 39.39 ± 7.18; p = 0.02), and coefficient of variation of standard deviation (19.96 ± 4.01 vs 24.75 ± 3.31; p = 0.003). No differences were found in relation to IEFVPTC. Conclusion: Computerized image analysis revealed differences in nuclear texture between NIFTP and IFVPTC, but not for IEFVPTC.


Assuntos
Adenocarcinoma Folicular , Carcinoma Papilar, Variante Folicular , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/genética , Cromatina , Humanos , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética
15.
Rev Med Suisse ; 17(739): 962-966, 2021 May 19.
Artigo em Francês | MEDLINE | ID: mdl-34009754

RESUMO

Anaplastic thyroid cancer (ATC) is among the most aggressive cancers with a median overall survival of 4 months and a disease-specific mortality of close to 100%. As soon as the diagnosis is suspected or established, urgent referral to an experienced multidisciplinary center is imperative. Chemotherapy has limited efficacy. Molecular analyses, together with the availability of novel targeted therapies and immunotherapies, now permit to improve outcomes. In particular, targeted therapy with dabrafenib and trametinib is indicated as first-line therapy for BRAF V600E-mutated ATC.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Anaplásico da Tireoide/diagnóstico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética
16.
Oncology ; 99(7): 422-432, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33878761

RESUMO

BACKGROUND: Medullary thyroid carcinoma (MTC) comprises 1-2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. METHODS: Relevant articles were identified using a systematic PubMed and Google Scholar search. RESULTS: Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. CONCLUSION: With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.


Assuntos
Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Testes Genéticos/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Biomarcadores Tumorais/sangue , Biópsia por Agulha Fina , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/cirurgia , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Ultrassonografia/métodos
17.
Jpn J Clin Oncol ; 51(7): 1051-1058, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33893504

RESUMO

BACKGROUND: Papillary thyroid cancer cells can express oestrogen receptor alpha, which is encoded by the ESR1 gene and may bind to oestrogen to induce the occurrence and development of papillary thyroid cancer. The BRAFV600E mutation is also an important biomarker for the occurrence and progression of papillary thyroid cancer. However, the association between the BRAFV600E mutation and oestrogen receptor alpha expression has not been identified. This study aims to investigate the association between ESR1 expression and the BRAFV600E mutation and its clinical significance. METHODS: Oestrogen receptor alpha and BRAFV600E proteins were detected by immunohistochemical staining of formalin-fixed paraffin-embedded thyroid tissues from 1105 patients with papillary thyroid cancer at our institution. Messenger RNA expression counts of ESR1 and clinicopathologic information were obtained from The Cancer Genome Atlas database. RESULTS: Oestrogen receptor alpha protein expression was significantly associated with BRAFV600E protein. The positive rate of oestrogen receptor alpha protein in papillary thyroid cancer patients was significantly higher in males, younger patients and patients with the multifocal type. In papillary thyroid cancer patients with positive BRAFV600E protein, oestrogen receptor alpha expression was significantly correlated with central lymph node metastasis. Data from the The Cancer Genome Atlas database also suggested that the ESR1 messenger RNA level was associated with the BRAFV600E mutation. Furthermore, classification analysis performed according to a tree-based classification method demonstrated that higher ESR1 messenger RNA expression indicated poorer overall survival in papillary thyroid cancer patients with the BRAFV600E mutation. CONCLUSIONS: The percentage of BRAFV600E mutations is increased in patients with higher ESR1 messenger RNA levels, and the BRAFV600E protein might be co-expressed with oestrogen receptor alpha, which could be an indicator of cervical lymph node metastasis and poor overall survival in patients with papillary thyroid cancer.


Assuntos
Receptor alfa de Estrogênio , Proteínas Proto-Oncogênicas B-raf , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
18.
J Int Med Res ; 49(4): 3000605211008325, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33906532

RESUMO

OBJECTIVE: To detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC. METHODS: FKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice. RESULTS: We revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice. CONCLUSIONS: The results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.


Assuntos
MicroRNAs , Proteínas de Ligação a Tacrolimo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Proteínas de Ligação a Tacrolimo/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(1): 191-195, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33899445

RESUMO

In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Animais , Carcinoma Papilar/genética , Humanos , Metástase Linfática , Camundongos , Mutação , Oncogenes , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
20.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803747

RESUMO

Differentiated thyroid cancers (DTC) are commonly and successfully treated with total thyroidectomy plus/minus radioiodine therapy (RAI). Medullary thyroid cancer (MTC) is only treated with surgery but only intrathyroidal tumors are cured. The worst prognosis is for anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC). Whenever a local or metastatic advanced disease is present, other treatments are required, varying from local to systemic therapies. In the last decade, the efficacy of the targeted therapies and, in particular, tyrosine kinase inhibitors (TKIs) has been demonstrated. They can prolong the disease progression-free survival and represent the most important therapeutic option for the treatment of advanced and progressive thyroid cancer. Currently, lenvatinib and sorafenib are the approved drugs for the treatment of RAI-refractory DTC and PDTC while advanced MTC can be treated with either cabozantinib or vandetanib. Dabrafenib plus trametinib is the only approved treatment by FDA for BRAFV600E mutated ATC. A new generation of TKIs, specifically for single altered oncogenes, is under evaluation in phase 2 and 3 clinical trials. The aim of this review was to provide an overview of the current and future treatments of thyroid cancer with regards to the advanced and progressive cases that require systemic therapies that are becoming more and more targeted on the molecular identity of the tumor.


Assuntos
Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Terapia de Alvo Molecular , Transdução de Sinais , Neoplasias da Glândula Tireoide/tratamento farmacológico , Microambiente Tumoral/imunologia
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