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Results for “Thyroid Cancer, Papillary”

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At least 19 recordsLinked to original sources
PubMed2026

Protective TGFβ2/SMAD3 axis identified by TWAS in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGFβ2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGFβ signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGFβ2/SMAD3 axis in PTC.

Humans↗
PubMed2026

Myeloid landscape of BRAF-mutant papillary thyroid cancer and thyroiditis.

Papillary thyroid cancer (PTC) is less aggressive when associated with lymphocytic thyroiditis (LT), even in the presence of oncogenic BRAF, including smaller tumours, less lymph node involvement and reduced extrathyroidal extension. To investigate possible immune mechanisms underlying this association, we compared the tumour microenvironment of PTC-BRAF with LT and that without LT using single-cell RNA sequencing (scRNA-seq). Single-cell libraries were generated from fresh and fixed tumour samples with post-dissociation viability >70% using the 10x Genomics Chromium Platform and sequenced on an Illumina NovaSeq 6000. We analysed scRNA-seq data from 11 PTC-BRAF tumours: four with LT (one publicly available sample) and seven without LT. Downstream analyses included quality control, batch correction, dimensionality reduction, and differential gene expression analysis. We found that neutrophils were the predominant myeloid cell type in PTCs without LT. Thyrocytes without LT showed significant expression of the neutrophil recruitment chemokine ECRG4. In the absence of LT, neutrophils expressed oncogenic genes with poor clinical outcomes. In contrast, thyrocytes from tumours with LT showed increased expression of MHC-II antigen presentation, consistent with effective immune surveillance. Thyrocytes and macrophages in the presence of LT showed enrichment of interferon gamma response pathways. Our data suggest that LT in thyroid cancer is associated with enhanced antigen presentation and fewer features of pro-tumourigenic innate immune activity. These results identify previously under-recognised innate immune cell population and associated transcriptomic features, which suggest new mechanisms to target immune treatments in PTC refractory to other therapies.

Humans↗
PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗
PubMed2026

Risk factors for lung metastasis in children and adolescent patients with papillary thyroid cancer: A retrospective cohort study.

BACKGROUND: Pediatric papillary thyroid cancer (pPTC) exhibits a higher incidence of lung metastasis (LM) compared to its adult counterpart. This study supplements the gap in pediatric management guidelines by exploring factors associated with LM in pPTC and characterizing relevant genetic alterations. METHODS: We retrospectively analyzed pPTC patients under 20 years who underwent initial surgery at our center between December 2008 and December 2022. Clinicopathological features, treatment approaches, outcomes, and target-gene sequencing were reviewed to identify risk factors and genetic variations. RESULTS: Among 114 pPTC cases, 17 developed LM. Risk factors associated with LM included younger age, male gender, larger tumor size, multifocality, extrathyroidal extension, lymphatic invasion, and the number of metastatic lymph nodes (NMLNs), with NMLNs > 14 identified as an independent predictor (OR = 18.20, p = 0.037). Treatment responses with radioiodine related to postoperative stimulated thyroglobulin (sTg) levels (p = 0.003). Genomic analysis identified 1007 somatic mutations, including in the BRAF, APC, RET, and ATM genes, with RET-NCOA4 fusions observed in the LM subgroup. CONCLUSION: LM is common in pPTC, and NMLNs > 14 is a critical risk indicator. The genetic profile, particularly RET mutations, highlights potential therapeutic targets. Further large-scale studies are needed to validate these findings.

Humans↗
PubMed2026

Value of TERT promoter mutations for early outcomes in papillary thyroid cancer.

Telomerase reverse transcriptase (TERT) promoter mutations are associated with aggressive clinicopathological features of papillary thyroid cancer (PTC). However, their independent prognostic value remains unclear. This study aimed to evaluate the prognostic significance of TERT promoter mutations (TPMs) in predicting early treatment outcomes and event-free survival (EFS) in patients with PTC. We retrospectively analyzed a prospective cohort; patients underwent surgery at a single tertiary referral center between 2019 and 2022. Patients underwent thyroidectomy, selective postoperative radioactive iodine ablation, and levothyroxine suppression therapy. Propensity score matching (PSM, 1:1) was applied to adjust for baseline clinicopathological differences. Of 10,642 patients with available molecular data, 115 (1.1%) harbored TPMs. After PSM, 90 matched pairs of patients with TERT-wild-type and TERT-mutant tumors were analyzed. Early treatment responses at 1 and 2 years post-treatment and EFS were evaluated. Early treatment responses did not differ significantly between groups at 1 year (P = 0.212) and 2 years (P = 0.571). However, patients with TERT-mutant tumors had fewer excellent responses and higher rates of structural incomplete response. During follow-up, the TERT-mutant group experienced more recurrences and one disease-specific death. Cumulative EFS was significantly poorer in the TERT-mutant group than in the TERT-wild-type group (P = 0.022). Despite their low prevalence, TPMs were independently associated with adverse oncological outcomes, including higher rates of recurrence and mortality. TPMs may serve as valuable prognostic markers for early risk stratification in PTC.

Humans↗
PubMed1979

[Papillary thyroid cancer lying within a toxic adenoma (author's transl)].

The association of hyperthyroidism and thyroid cancer is rare. The commonest finding is multilobular goitres. When a toxic adenoma is associated with a thyroid cancer they are usually clearly separate lesions. A thyroid cancer lying within a toxic adenoma, as in this case, is a much rarer occurrence, and a review of the published literature suggests that the relatively frequent association of the two lesions is fortuitous. The possibility of a cancer occurring near, or within a toxic adenoma, is an argument in of surgical treatment of these formations.

Adenoma↗
PubMed2026

MicroRNA-181a-5p promotes papillary thyroid carcinoma progress via the PTEN/AKT pathway.

The objective of this investigation was to determine the expression profile and latent mechanism of microRNA-181a-5p (miR-181a-5p) in the genesis and progression of papillary thyroid cancer (PTC). MiR-181a-5p was discovered to be upregulated in PTC tissues and cells in this study, as confirmed by RT‒qPCR and The Cancer Genome Atlas database. Notably, in PTC patients, the miR-181a-5p level was linked to tumor size and thyroid capsule invasion. A series of experiments demonstrated that miR-181a-5p upregulation in PTC cells notably enhanced proliferation, motility, and invasion, whereas suppressing miR-181a-5p hindered these functions. Western blotting revealed that miR-181a-5p suppressed PTEN expression, boosting the activation of phosphorylated AKT (P-AKT). According to predictive bioinformatics research and luciferase reporter gene tests, miR-181a-5p may target a specific binding site on the PTEN 3'UTR. To sum up, this study indicated that miR-181a-5p promoted PTC progression through the PTEN/Akt pathway. This investigation reveals a potential mechanism for PTC progression and provides a foundation for clinical therapies.

MicroRNAs↗
PubMed2025

Mechanisms of resistance to RET-directed therapies.

The association between RET and multiple endocrine neoplasia type 2 was established in 1993 and remains one of the very few oncogenes for which distinct phenotypes (medullary thyroid cancer or pheochromocytoma) are associated with the same hot-spot variants occurring in either germline or somatic DNA. Somatic RET fusion events have also been described in several cancers, including papillary thyroid cancer, non-small-cell lung cancer, breast cancer, salivary gland cancer and pancreatic cancer. Highly selective RET inhibitors have improved outcomes in RET-altered cancers and have been well-tolerated. Nevertheless, primary and acquired drug resistance has been observed, arising from distinct genomic alterations either in RET (on-target resistance) or via alternate oncogenic pathways (bypass resistance). The same mechanisms of resistance have been observed across multiple cancer types, which implies RET-altered cancers evolve away from RET addiction via stochastic subclonal events. Understanding these mechanisms is crucial for identifying therapeutic opportunities to overcome resistance. Successful treatment targeting bypass oncogenes has been reported in several instances, at least for short-term outcomes; in contrast, although several compounds have been reported to overcome on-target RET alterations, none have yet been translated into routine clinical practice and this remains an area of urgent clinical need.

Animals↗
PubMed1978

Differentiated thyroid cancer following radioiodide 131I therapy of hyperthyroidism--a case report.

Differentiated (papillary) thyroid cancer was detected 17 years following radioiodide 131I treatment for toxic multinodular goiter. 21 cases of thyroid cancers with previous 131 I therapy for hyperthyroidism were summarised. This combination is rare compared to the incidence of thyroid cancers following external irradiation. This may be due to higher absorbed dose to thyroid in 131I treatment.

Adolescent↗
PubMedDate not supplied

An electron-microscopic study of human thyroid cancer.

Authors studied the ultrastructural characteristics of the following thyroid cancer: papillary carcinoma, follicular carcinoma, undifferentiated carcinoma and medullary carcinoma. Some specific ultrastructural-functional correlations for each type of thyroid cancer could be established. Papillary and follicular carcinoma had some common features: larger nuclei than in benign lesions, a highly increased number of mitochondria, a reduced endoplasmic reticulum, cell junctions between the cells and an intact basal lamina. In addition, papillary carcinoma presented stage I and stage II nuclear inclusions, and nuclear invaginations that contained cytoplasm. The higher malignancy of follicular carcinoma compared with that of papillary carcinoma was assigned to less differentiated areas corresponding to the compact fields. Undifferentiated carcinoma consisted of large pleomorphic cells (spindle and giant cells) with abundant mitochondria, a flat rough endoplasmic reticulum, scanty secretory granules and lysosomes, cell junctions, all suggesting their common epithelial origin. Ultrastructure of medullary carcinoma contributed to the explanation of the amyloid origin and of granule types in correlation with hormone storage in cells.

Adenocarcinoma↗
PubMed2025

Genomic testing for RET in the clinic: UK and global perspective.

RET is a key oncogene in neuroendocrine cancer. Pathogenic germline variants lead to multiple different phenotypes, including multiple endocrine neoplasia type 2, medullary thyroid cancer (MTC), Hirschsprung disease and kidney malformations. Pathogenic somatic variants are also associated with MTC, and RET rearrangements are observed in papillary thyroid cancer, non-small cell lung cancer and pan-cancer syndromes. Testing for both germline and somatic variants is now feasible in everyday clinical practice, and their identification has important clinical consequences, both for affected individuals and their families. This mini-review will discuss current germline and somatic testing strategies in the UK and worldwide, as well as reporting and test outcomes (including variants of uncertain significance or incidental findings). It will explore actions following identification of a pathogenic germline variant, including predictive, reproductive and childhood testing, and somatic testing of RET variants in solid tumours informing personalised cancer treatment. Finally, it will discuss the challenge of delivering rapid and equitable access to genomic testing to ensure that all individuals can benefit promptly and appropriately to improve clinical outcomes.

Humans↗
PubMed1978

The role of external radiation in the management of papillary and follicular thyroid cancer.

Review of 137 patients with differentiated thryroid carcinoma (82 papillary and 55 follicular) demonstrates that external radiation in moderate dosage eradicates microscopic disease. Its use could lead to a decrease in surgical complications by avoiding unnecessarily radical attempts at removing all potential microscopic disease. Gross tumor also responds favorably to external radiation, but its very slow regression rate has led to the misconception that external radiation is ineffective in the treatment of these cancers. Both radioiodine and thyroid hormone play an important role in the management of differentiated thyroid cancers, but their effectiveness should not be overestimated.

Adenocarcinoma↗
PubMed2026

TCGA-based identification of prognostic biomarkers and candidate traditional Chinese medicine compounds in papillary thyroid carcinoma: An observational study.

This study aimed to identify prognostic genes associated with papillary thyroid carcinoma (PTC) and explore candidate traditional Chinese medicine (TCM) compounds using integrated bioinformatics and molecular docking. In this observational study, PTC gene expression profiles and clinical data were obtained from The Cancer Genome Atlas. Differentially expressed genes were screened using differential-expression sequencing (DESeq2), followed by protein-protein interaction network analysis to identify hub genes. Their expression, diagnostic value, immune relevance, prognostic significance, protein-level validation, and single-cell distribution were assessed using gene expression profiling interactive analysis, receiver operating characteristic analysis, immune infiltration analysis, Kaplan-Meier survival analysis, the human protein atlas, and single-cell RNA-sequencing data. Candidate TCM compounds were predicted using symptom mapping (SymMap) and the TCM Systems Pharmacology Database and Analysis Platform, and molecular docking was performed to evaluate potential ligand-target interactions. Five hub genes, colony-stimulating factor 2, apolipoprotein E, fibronectin 1 (FN1), collagen type I alpha 1 chain (COL1A1), and intercellular adhesion molecule 1, were identified and found to be significantly upregulated in PTC tissues, with diagnostic value in receiver operating characteristic analysis. Immune infiltration analysis showed associations with macrophages, dendritic cells, and T helper 1 cells, whereas single-cell analysis demonstrated heterogeneous expression across immune and stromal cell populations, including fibroblasts. Higher FN1 and COL1A1 expression was associated with poorer outcomes. Immunohistochemistry supported the expression patterns, while single-cell analysis provided exploratory cell-type-level context for the cellular distribution of selected genes. Ginseng and Smilax glabra were predicted as common candidate TCMs, and docking suggested favorable binding between their active compounds and selected hub targets. Colony-stimulating factor 2, apolipoprotein E, FN1, COL1A1, and intercellular adhesion molecule 1 may be biologically relevant hub genes in PTC, while FN1 and COL1A1 may have prognostic value. Predicted TCM compounds provide preliminary computational evidence for possible compound-target interactions, requiring experimental and clinical validation.

Female↗
PubMed2012

RETRACTED: Identification of sumoylation sites in CCDC6, the first identified RET partner gene in papillary thyroid carcinoma, uncovers a mode of regulating CCDC6 function on CREB1 transcriptional activity.

CCDC6 was originally identified in chimeric genes as caused by chromosomal translocation involving the RET protooncogene in some thyroid tumors. Recognised as a 65 kDa pro-apoptotic phosphoprotein, CCDC6 has been enrolled as an ATM substrate that contribute to protect genome integrity by modulating PP4c activity in response to genotoxic stress. Recently, CCDC6 has been identified as a repressor of CREB1-dependent transcription. Sumoylation has emerged as an important mechanism in transcriptional control. Here, we report the identification and characterization of three sites of sumoylation in CCDC6 (K74, K266 and K424) which are highly conserved in vertebrates. We demonstrate that the post-translational modifications by SUMO2 constrain most of the CCDC6 protein in the cytosol and affect its functional interaction with CREB1 with a decrease of CCDC6 repressive function on CREB1 transcriptional activity. Indeed, the impairment of functional outcome of sumoylated CCDC6 is obtained knocking down all three the sumoylation sites. Interestingly, in thyroid cells the SUMO2-mediated CCDC6 post-translational modifications are induced by Forskolin, a cAMP analog. Signal transduction via the cAMP pathway is known to be ubiquitous and represents a major line of communication between many organisms and their environment. We believe that CCDC6 could be an important player in the dynamics of cAMP signaling by fine regulating CREB1 transcriptional activity in normal and transformed thyroid cells.

Animals↗
PubMed1978

[Papillary cancer of the thyroid: biological behaviour and therapeutic planning (author's transl)].

Out of about 600 thyroid tumors treated from 1956 to 1976, a series of 216 papillary cancers were selected at an hystological reevaluation. The correlation between survival rate and clinical features as well as extent of the primary tumor and presence of regional and distant metastases was investigated. An improvement in results may be expected by more extensive surgery on the thyroid, adequate post-operative X-ray and 131I radiation therapy, associated with suppression of TSH production in case of endocrine-dependent tumors.

Adolescent↗