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The Journal of Clinical Endocrinology... Oct 2023Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular...
CONTEXT
Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular thyroid carcinoma (FTC) but is poor for poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Among PTCs, the prognosis is more favorable for follicular (FV-PTC) and classic (CV-PTC) than for tall cell (TCV-PTC), and solid (SV-PTC) variants.
OBJECTIVE
To associate histotypes and variants of thyroid carcinoma with ultrasound and cytological features.
METHODS
Histology of 1018 benign tumors and 514 PTC (249 CV, 167 FV, 49 TC, 34 SV, and 15 other variants), 52 NIFT-P, 50 FTC, 11 PDTC, and 3 ATC was correlated with fine-needle aspiration biopsy categories (Italian classification: TIR1, TIR2, TIR3A, TIR3B, TIR4, and TIR5) and ultrasound features at the Endocrinology Unit, University Hospital of Pisa. In total, 1117 patients with thyroid nodule(s) who underwent thyroidectomy were included.
RESULTS
Of PTC, 36.3% had indeterminate cytology (TIR3A or TIR3B), 56.6% were suspicious for malignancy or malignant (TIR4 or TIR5); 84.0% FTC and 69.3% NIFT-P were TIR3A or TIR3B; 72.5% FV-PTC and 73.6% SV-PTC were TIR3A or TIR3B; 79.9% CV-PTC and 95.9% TCV-PTC were TIR4 or TIR5. The association of a hypoechoic pattern, irregular margins, and no microcalcifications was more frequent in TCV-PTC than in CV-PTC (P = .02, positive predictive value = 38.9%; negative predictive value = 85.5%).
CONCLUSION
At cytology, most FTC, NIFT-P, FV-PTC, and SV-PTC were indeterminate, most CV-PTC and TCV-PTC were suspicious for malignancy or malignant. Ultrasound can be helpful in ruling out TCV-PTC.
Topics: Humans; Thyroid Nodule; Thyroid Neoplasms; Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Thyroid Carcinoma, Anaplastic; Retrospective Studies
PubMed: 37265229
DOI: 10.1210/clinem/dgad313 -
Endocrinology and Metabolism (Seoul,... Aug 2023Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each...
BACKGRUOUND
Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.
METHODS
We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment.
RESULTS
Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status.
CONCLUSION
The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Proto-Oncogene Proteins B-raf; Carcinoma, Papillary; Mutation; Phenotype; Tumor Microenvironment
PubMed: 37461149
DOI: 10.3803/EnM.2023.1702 -
Molecular and Cellular Biochemistry Sep 2023To perform bioinformatics analysis on the papillary thyroid carcinoma (PTC) gene chip dataset to explore new biological markers for PTC. The gene expression profiles of...
To perform bioinformatics analysis on the papillary thyroid carcinoma (PTC) gene chip dataset to explore new biological markers for PTC. The gene expression profiles of GSE3467 and GSE6004 chip data were collected by GEO2R, and the differentially expressed genes (DEGs) were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-protein interaction (PPI) relationship analysis was achieved using STRING, and the hub genes were obtained using the Cytoscape software. GEPIA was used to validate the expressions of the hub genes in the normal and tumor tissues and to conduct survival analyses. Pertinent genetic pathology results were fetched using the HPA database. Finally, the key genes were clinically verified by reverse transcription-polymerase chain reaction. 97 genes were jointly up-regulated and 107 genes were jointly down-regulated in GSE3467 and GSE6004. GO function enrichment analysis revealed that the DEGs were involved in the regulation of calcium ion transport into cytosol, integrin binding, and cell adhesion molecule binding. KEGG pathway enrichment analysis indicated that the DEGs were chiefly associated with thyroid cancer and non-small cell lung cancer. According to the PPI network, 30 key target genes were identified. Only the expressions of ANK2, TLE1, and TCF4 matched between the normal and tumor tissues, and were associated with disease prognosis. When compared with the normal thyroid tissues, the protein and mRNA expressions of ANK2, TLE1, and TCF4 were down-regulated in PTC. Significant differences exist in overall gene expression between the thyroid tissues of patients with PTC and those of healthy people. Furthermore, the differential genes ANK2, TLE1, and TCF4 are expected to be reliable molecular markers for the mechanism study and diagnosis of PTC.
Topics: Humans; Thyroid Cancer, Papillary; Carcinoma, Non-Small-Cell Lung; Gene Regulatory Networks; Lung Neoplasms; Thyroid Neoplasms; Biomarkers, Tumor; Computational Biology; Gene Expression Regulation, Neoplastic; Gene Expression Profiling
PubMed: 36635603
DOI: 10.1007/s11010-022-04606-x -
Theranostics 2024Periostin (POSTN) is a critical extracellular matrix protein in various tumor microenvironments. However, the function of POSTN in thyroid cancer progression remains...
Periostin (POSTN) is a critical extracellular matrix protein in various tumor microenvironments. However, the function of POSTN in thyroid cancer progression remains largely unknown. and knock-out mice and orthotopic mouse models were used to determine the role of POSTN on papillary thyroid tumor progression. Immunofluorescence, cell co-culture, fluorescence hybridization, chromatin immunoprecipitation assay, recombinant protein and inhibitor treatment were performed to explore the underlying mechanisms of POSTN-promoted papillary thyroid tumor growth. POSTN is up-regulated in papillary thyroid tumors and negatively correlates with the overall survival of patients with thyroid cancer. Cancer-associated fibroblast (CAF)-derived POSTN promotes papillary thyroid tumor growth and . POSTN deficiency in CAFs significantly impairs CAF-promoted papillary thyroid tumor growth. POSTN promotes papillary thyroid tumor cell proliferation and IL-4 expression through integrin-FAK-STAT3 signaling. In turn, tumor cell-derived IL-4 induces the activation of CAFs and stimulates POSTN expression by activating STAT6. We reveal the crucial role of CAF-derived POSTN and tumor cell-derived IL-4 in driving the development of papillary thyroid tumors through the POSTN-integrin-FAK-STAT3-IL-4 pathway in tumor cells and IL-4-STAT6-POSTN signaling in CAFs. Our findings underscore the significance of POSTN and IL-4 as critical molecular mediators in the dynamic interplay between CAFs and tumor cells, ultimately supporting the growth of papillary thyroid tumors.
Topics: Animals; Thyroid Cancer, Papillary; STAT3 Transcription Factor; Cancer-Associated Fibroblasts; Cell Adhesion Molecules; Mice; Humans; Signal Transduction; Thyroid Neoplasms; Mice, Knockout; Cell Line, Tumor; Cell Proliferation; Tumor Microenvironment; Interleukin-4; Integrins; Focal Adhesion Kinase 1; Periostin
PubMed: 38773979
DOI: 10.7150/thno.94207 -
The British Journal of Surgery Nov 2023Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent...
BACKGROUND
Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent outcomes of paediatric thyroid surgery in Germany and Austria.
METHODS
Patients aged less than or equal to 18 years who underwent thyroid surgery and were prospectively documented in the StuDoQ|Thyroid registry between March 2017 and August 2022 were studied.
RESULTS
In total, 604 patients from 90 institutions were included. The mean age was 15.4 years and 75 per cent of patients were female. The most frequent benign pathologies were nodular goitre (35.6 per cent), follicular adenoma (30.1 per cent), and Graves' disease (28.5 per cent). Among 126 thyroid malignancies, papillary thyroid carcinoma was diagnosed in 77.8 per cent of patients, follicular thyroid carcinoma was diagnosed in 10.3 per cent of patients, and medullary thyroid carcinoma was diagnosed in 8.7 per cent of patients. Lymph node metastases were found in 45.9 per cent of patients with papillary thyroid carcinoma and in 36.4 per cent of patients with medullary thyroid carcinoma. Vascular invasion was found in 62.9 per cent of patients with follicular thyroid carcinoma. The mean tumour diameters were 18, 42, and 13 mm in patients with papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma respectively. Early postoperative recurrent laryngeal nerve injury was seen in 27 of 556 patients (4.9 per cent) (22 of 617 (3.6 per cent) nerves at risk with intermittent intraoperative nerve monitoring and 5 of 237 (2.1 per cent) nerves at risk with continuous intraoperative nerve monitoring). Persistent recurrent laryngeal nerve injury was documented in 4 of 556 patients (0.7 per cent). Early postoperative hypoparathyroidism correlated with Graves' disease, thyroid carcinoma, and lymph node dissection.
CONCLUSION
Papillary thyroid carcinoma and follicular thyroid carcinoma in children were often advanced at presentation. Persistent or recurrent lymph node metastases were mainly seen in papillary thyroid carcinoma. Overall survival was excellent, but longer follow-up is needed.
Topics: Humans; Child; Female; Adolescent; Male; Austria; Thyroid Cancer, Papillary; Lymphatic Metastasis; Recurrent Laryngeal Nerve Injuries; Thyroidectomy; Retrospective Studies; Thyroid Neoplasms; Adenocarcinoma, Follicular; Graves Disease
PubMed: 37758484
DOI: 10.1093/bjs/znad255 -
Frontiers in Endocrinology 2023We aimed to identify the clinical factors associated with lymph node metastasis (LNM) based on ultrasound characteristics and clinical data, and develop a nomogram for...
OBJECTIVE
We aimed to identify the clinical factors associated with lymph node metastasis (LNM) based on ultrasound characteristics and clinical data, and develop a nomogram for personalized clinical decision-making.
METHODS
A retrospective analysis was performed on 252 patients with papillary thyroid carcinoma (PTC). The patient's information was subjected to univariate and multivariate logistic regression analyses to identify risk factors. A nomogram to predict LNM was established combining the risk factors. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curve, calibration curve, cross-validation, decision curve analysis (DCA), and clinical impact curve.
RESULTS
There are significant differences between LNM and non-LNM groups in terms of age, sex, tumor size, hypoechoic halo around the nodule, thyroid capsule invasion, lymph node microcalcification, lymph node hyperechoic area, peak intensity of contrast (PI), and area under the curve (AUC) of the time intensity curve of contrast (<0.05). Age, sex, thyroid capsule invasion, lymph node microcalcification were independent predictors of LNM and were used to establish the predictive nomogram. The ROC was 0.800, with excellent discrimination and calibration. The predictive accuracy of 0.757 and the Kappa value was 0.508. The calibration curve, DCA and calibration curve demonstrated that the prediction model had excellent net benefits and clinical practicability.
CONCLUSION
Age, sex, thyroid capsule invasion, and lymph node microcalcification were identified as significant risk factors for predicting LNM in patients with PTC. The visualized nomogram model may assist clinicians in predicting the likelihood of LNM in patients with PTC prior to surgery.
Topics: Humans; Thyroid Cancer, Papillary; Lymphatic Metastasis; Retrospective Studies; Risk Factors; Calcinosis; Factor Analysis, Statistical; Thyroid Neoplasms
PubMed: 38027220
DOI: 10.3389/fendo.2023.1287593 -
Frontiers in Endocrinology 2023Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features,...
Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm () to 502 cases annotated by The Cancer Genome Atlas Project to derive an accurate molecular prognostic classifier. Unsupervised analysis of the 82 genes that were most closely associated with recurrence after surgery enabled the identification of three unique molecular subtypes. One subtype had a high recurrence rate, an immunosuppressed microenvironment, and enrichment of the EZH2-HOTAIR pathway. Two other unique molecular subtypes with a lower rate of recurrence were identified, including one subtype with a paucity of BRAF mutations and a high rate of RAS mutations. The genomic risk classifier, in addition to tumor size and lymph node status, enabled effective prognostication that outperformed the American Thyroid Association clinical risk stratification. The genomic classifier we derived can potentially be applied preoperatively to direct clinical decision-making. Distinct biological features of molecular subtypes also have implications regarding sensitivity to radioactive iodine, EZH2 inhibitors, and immune checkpoint inhibitors.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Carcinoma, Papillary; Iodine Radioisotopes; Proto-Oncogene Proteins B-raf; Genomics; Tumor Microenvironment
PubMed: 37772080
DOI: 10.3389/fendo.2023.1220617 -
Hormone and Metabolic Research =... Sep 2023Suppression of TSH levels associated with levothyroxine treatment is a known risk factor for fracture. However, it is unclear whether patients with papillary thyroid...
Suppression of TSH levels associated with levothyroxine treatment is a known risk factor for fracture. However, it is unclear whether patients with papillary thyroid carcinoma (PTC) have a higher risk of vertebral fracture (VF) before TSH suppression. The aim of the study was to examine whether the risk of VF is higher in PTC than in healthy subjects. A hospital-based, matched case-control study was conducted comparing PTC and healthy individuals. We enrolled 43 postoperative patients with PTC scheduled for radioiodine therapy and 43 age- and sex-matched healthy controls. Serum and urinary biological parameters, bone mineral density (BMD), and presence of VFs were evaluated in both groups. We compared these indices using χ2 and Mann-Whitney U-test and analyzed the association between PTC and VF by logistic regression analysis. The PTC group had higher BMI, HbA1c and phosphorus, and lower intact PTH than the control group. Lumbar and femoral neck BMD did not differ between the two groups. Prevalence of VFs was significantly higher in the PTC group (44.1%) than in the control group (16.3%). Multivariate logistic regression analyses adjusted for age, sex, and BMI identified PTC as being associated with the presence of VFs (odds ratio, 5.63; 95% confidence interval: 1.82 to 17.5). This relationship remained significant after additional adjustment for HbA1c and BMD. There is an association between PTC and a risk of VF independent of sex, BMI, glucose metabolism, and BMD, suggesting the importance of fracture risk assessment before TSH suppression.
Topics: Humans; Spinal Fractures; Thyroid Cancer, Papillary; Case-Control Studies; Glycated Hemoglobin; Iodine Radioisotopes; Bone Density; Thyroid Neoplasms; Thyrotropin
PubMed: 37068493
DOI: 10.1055/a-2059-8830 -
Annals of Medicine Dec 2023This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer...
OBJECTIVE
This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA).
METHODS
The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal tissues were retrieved from The Cancer Genome Atlas (TCGA)-THCA dataset. The Pearson test was utilized to identify potential m6A-associated lncRNAs ( < 0.001 and Pearson correlation coefficient > 0.4). Quantitative real-time polymerase chain reaction was performed to verify the expression levels of lncRNAs in tissues. MTT, EdU, colony formation and wound-healing assays were performed to determine the functions of m6A-associated lncRNAs in THCA cell proliferation and metastasis.
RESULTS
M6A-associated lncRNAs were identified in three cluster groups. A significant survival difference was found among them, with cluster 1 patients showing worse survival. Moreover, lower immune and estimate scores were correlated to poorer prognosis, and CD8+ T cell and memory CD4+ T cell levels were increased in cluster 1. Cluster 2, with better overall survival, had high expression of PD-L1 and CTLA-4. Eleven of the m6A-associated lncRNAs were screened to establish the risk model, including AC007365.1, AC008555.1, AC040160.1, AC064807.1, AC126773.4, AL023583.1, AL512306.2, EIF2AK3-DT, LINC00667, LYPLAL1-DT and MIR181A2HG. Based on the median risk score, THCA patients were stratified into low-risk and high-risk groups. Overall survival analysis showed a dramatic difference between the two groups. qRCR was performed to verify the expression levels of lncRNA (LYPLAL1-DT, EIF2AK3-DT and MIR181A2HG) in THCA and adjacent normal tissues. Furthermore, functional experiments showed that knockdown of MIR181A2HG obviously inhibited the proliferation and migration of papillary thyroid cancer (PTC) cells , whereas LYPLAL1-DT overexpression promoted PTC cell proliferation and migration.
CONCLUSIONS
Eleven of the m6A-associated lncRNAs were identified as a risk model to predict clinical outcomes and provide a novel and efficient immunotherapeutic strategy for THCA patients.Key messagesm6A-associated lncRNAs can be used to predict the clinical outcomes of thyroid cancer patients.An m6A-associated lncRNAs risk model, which can accurately evaluate the immune status and risk stratification in individual thyroid cancer patients, was established.Knockdown/overexpression of representative lncRNAs in the risk model significantly affected the proliferation and migration of papillary thyroid cancer cells.
Topics: Humans; RNA, Long Noncoding; Thyroid Cancer, Papillary; Thyroid Neoplasms; Prognosis; CD8-Positive T-Lymphocytes; Tumor Microenvironment
PubMed: 36974635
DOI: 10.1080/07853890.2023.2192049 -
Journal of Cancer Research and Clinical... Oct 2023Thyroid carcinoma (THCA) is a common type of cancer worldwide, and its incidence has been increasing in recent years. Disulfidptosis, a recently defined form of...
BACKGROUND
Thyroid carcinoma (THCA) is a common type of cancer worldwide, and its incidence has been increasing in recent years. Disulfidptosis, a recently defined form of metabolic-related regulated cell death (RCD), has been shown to play a sophisticated role in antitumor immunity. However, its mechanisms and functions are still poorly understood and the association between disulfidptosis and the prognosis of patients with papillary thyroid carcinoma remains to be elucidated. This study aims to investigate the connection between disulfidptosis and the prognosis of thyroid cancer, while also developing a prognostic index based on disulfidptosis genes.
MATERIALS AND METHODS
We utilized 24 genes associated with disulfidptosis to create the classification and model. To gather data, we sourced gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA database for patients with thyroid cancer. Additionally, we obtained single-cell transcriptome data GSE184362 from the Gene Expression Omnibus (GEO) database for further analysis.
RESULTS
In this study, we utilized 24 genes associated with disulfidptosis to identify two distinct groups with different biological processes using non-negative matrix factorization (NMF). Our findings showed that Cluster 1 is associated with chemokines, interleukins, interferons, checkpoint genes, and other important components of the immune microenvironment. Moreover, cluster 1 patients with high IPS scores may be more sensitive to immunotherapy. We also provide drug therapeutic strategies for each cluster patients based on the IC50 of each drug. The Enet model was chosen as the optimal model with the highest C-index and showed that patients with high risk had a worse prognosis and weak cell-to-cell interactions in THCA. Finally, we established a nomogram model based on multivariable cox and logistic regression analyses to predict the overall survival of THCA patients.
CONCLUSION
This research provides new insight into the impact of disulfidptosis on THCA. Through a thorough examination of disulfidptosis, a new classification system has been developed that can effectively predict the clinical prognosis and drug sensitivity of THCA patients.
Topics: Humans; DNA Copy Number Variations; Prognosis; Thyroid Neoplasms; Thyroid Cancer, Papillary; Immunotherapy; Tumor Microenvironment
PubMed: 37347261
DOI: 10.1007/s00432-023-05006-4