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Background: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48–0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3–4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16–2.04), 1.14 (95% CI: 0.82–1.58), 1.66 (95% CI: 1.40–1.97), 1.53 (95% CI: 1.35–1.75), and 1.24 (95% CI: 1.11–1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51–0.81) for CNND, 0.83 (95% CI: 0.73–0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58–0.86) for ETE, 0.84 (95% CI: 0.75–0.94) for AJCC Stage 3–4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66–1.90, p = 0.67) and 0.60 (95% CI: 0.28–1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer. [ABSTRACT FROM AUTHOR]

Objective: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/ recurrence. Methods: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. Results: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031]. Conclusion: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC. [ABSTRACT FROM AUTHOR]

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice. [ABSTRACT FROM AUTHOR]

Purpose: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown. Patients and methods: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC. Results: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes. Conclusion: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the expression of microRNAs (miRNAs) -146b-3p, -221-5p, -222-3p, and -21a-3p and the methylation pattern of the thyroid-stimulating hormone receptor (TSHR) gene in blood plasma samples from papillary thyroid cancer (PTC) patients before and after thyroidectomy compared to healthy controls (HCs). This study included 103 participants, 46 PTC patients and 57 HCs, matched for gender and age. Significantly higher preoperative expression levels of miRNAs and TSHR methylation were determined in the PTC patients compared to HCs. Post-surgery, there was a notable decrease in these biomarkers. Elevated TSHR methylation was linked to larger tumor sizes and lymphovascular invasion, while increased miRNA-222-3p levels correlated with multifocality. Receiver operating characteristic (ROC) analysis showed AUCs below 0.8 for all candidate biomarkers. However, significant changes in the expression of all analyzed miRNAs and TSHR methylation levels indicate their potential to differentiate PTC patients from healthy individuals. These findings suggest that miRNAs and TSHR methylation levels may serve as candidate biomarkers for early diagnosis and monitoring of PTC, with the potential to distinguish PTC patients from healthy individuals. Further research is needed to validate these biomarkers for clinical application. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is the most frequent endocrine cancer. Aberrant expression of miRNAs can increase the risk of thyroid cancer. We aimed to investigate the miR-126-3p and miR-146a-5p plasma levels in patients with thyroid nodules and to identify their associations with clinicopathological characteristics, and progression of PTC. Methods: We enrolled forty healthy control and forty patients with thyroid nodules; benign thyroid nodules (BTN), (n=30), and PTC(n=10). We analyzed miR-126-3p and miR-146a-5p levels by using real-time PCR. Results: miR-126-3p expression level was downregulated in PTC patients (0.40±0.11) compared with BTN (0.58±0.12) and healthy subjects (0.87±0.31), P<0.001*. Regarding miR-146a-5p, its level was upregulated in PTC patients (4.59±1.61) compared with BTN (3.77±0.96) and healthy subjects (0.99±0.41), Additionally, miR-126-3p and miR-146b-5p levels were significantly associated with tumor progression, lymph node metastasis, TNM staging, and thyroid function tests. The diagnostic power of miR-126-3p in the prediction of PTC, the AUC was 0.860 with a sensitivity of 60 % and specificity of 87.3% at cutoff values =0.49. miR-146a-5p level in the prediction of PTC, the AUC was 0.742 with a sensitivity of 80 % and specificity of 74.3% at cutoff values =3.4. Conclusions: miR-146a-5p and miR-126-3p levels were dysregulated in patients with PTC compared to patients with BTN and the control group. The dysregulated miRNAs were associated with clinicopathological features of PTC. [ABSTRACT FROM AUTHOR]

[Display omitted] • The suspicious ultrasonography features are related to immune response in thyroid cancer. • The features were also related to epithelial to mesenchymal transition (EMT). • Immune response and EMT were related to aggressive clinical behaviors. • Immune response and EMT reflected in the decision by radiologists and convolutional neural networks. Ultrasonography (US) features of papillary thyroid cancers (PTCs) are used to select nodules for biopsy due to their association with tumor behavior. However, the molecular biological mechanisms that lead to the characteristic US features of PTCs are largely unknown. This study aimed to investigate the molecular biological mechanisms behind US features assessed by radiologists and three convolutional neural networks (CNN) through transcriptome analysis. Transcriptome data from 273 PTC tissue samples were generated and differentially expressed genes (DEGs) were identified according to US feature. Pathway enrichment analyses were also conducted by gene set enrichment analysis (GSEA) and ClusterProfiler according to assessments made by radiologists and three CNNs - CNN1 (ResNet50), CNN2 (ResNet101) and CNN3 (VGG16). Signature gene scores for PTCs were calculated by single-sample GSEA (ssGSEA). Individual suspicious US features consistently suggested an upregulation of genes related to immune response and epithelial-mesenchymal transition (EMT). Likewise, PTCs assessed as positive by radiologists and three CNNs showed the coordinate enrichment of similar gene sets with abundant immune and stromal components. However, PTCs assessed as positive by radiologists had the highest number of DEGs, and those assessed as positive by CNN3 had more diverse DEGs and gene sets compared to CNN1 or CNN2. The percentage of PTCs assessed as positive or negative concordantly by radiologists and three CNNs was 85.6% (231/273) and 7.1% (3/273), respectively. US features assessed by radiologists and CNNs revealed molecular biologic features and tumor microenvironment in PTCs. [ABSTRACT FROM AUTHOR]

Purpose: Multifocal disease in PTC is associated with an increased recurrence rate. Multifocal disease (MD) is underdiagnosed with the current gold standard of pre-operative ultrasound staging. Here, we evaluate the use of EMI-137 targeted molecular fluorescence-guided imaging (MFGI) and spectroscopy as a tool for the intra-operative detection of uni- and multifocal papillary thyroid cancer (PTC) aiming to improve disease staging and treatment selection. Methods: A phase-1 study (NCT03470259) with EMI-137 was conducted to evaluate the possibility of detecting PTC using MFGI and quantitative fiber-optic spectroscopy. Results: Fourteen patients underwent hemi- or total thyroidectomy (TTX) after administration of 0.09 mg/kg (n = 1), 0.13 mg/kg (n = 8), or 0.18 mg/kg (n = 5) EMI-137. Both MFGI and spectroscopy could differentiate PTC from healthy thyroid tissue after administration of EMI-137, which binds selectively to MET in PTC. 0.13 mg/kg was the lowest dosage EMI-137 that allowed for differentiation between PTC and healthy thyroid tissue. The smallest PTC focus detected by MFGI was 1.4 mm. MFGI restaged 80% of patients from unifocal to multifocal PTC compared to ultrasound. Conclusion: EMI-137-guided MFGI and spectroscopy can be used to detect multifocal PTC. This may improve disease staging and treatment selection between hemi- and total thyroidectomy by better differentiation between unifocal and multifocal disease. Trial registration: NCT03470259 [ABSTRACT FROM AUTHOR]

The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease. A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations. Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features. A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases. [ABSTRACT FROM AUTHOR]

Background: Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. Materials and methods: Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. Results: The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01). Conclusion: These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). Methods: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. Results: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p >.05), and significantly outperformed the radiomics model (p <.05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. Conclusion: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC. [ABSTRACT FROM AUTHOR]

The association of clinical, pathological, and immunohistochemical characteristics of papillary thyroid cancer with cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center. According to multivariate analysis, the independent predictors of fatal outcome within 10 years after surgery in patients living in Altai region are nuclear pattern of Hsp70 expression, thyroid capsular invasion, Ki-67 expression index >7%, and patient's age >45 years for men and >50 years for women. The prognostic model based on these features contributes to a significant improvement in the individual prognostic performance for papillary thyroid cancer in the modeling sample. The model has high statistical significance (χ2=64.73; p<0.001) and discriminative power (AUC=0.950, prediction accuracy 88.5%). [ABSTRACT FROM AUTHOR]

Objective: To evaluate sanitary techniques for radical thyroid cancer surgery via the transaxillary approach without inflation single-port endoscopic surgery (TAWISES) and the conventional open anterior cervical approach (COACAS) in a controlled manner. Methods: This work was a retrospective analysis of the clinical data of 60 patients admitted to our hospital for unilateral radical thyroid cancer surgery between 01/2021 and 12/2022. The control group underwent COACAS (30 patients), and the experimental group underwent TAWISES (30 patients). The patients' operative time, intraoperative bleeding volume, 24-h postoperative pain index, drainage tube carrying time, hospitalization duration and complication rate were compared and analyzed. The patients were followed up for 3, 6 and 12 months postoperatively and evaluated based on numbness, muscular tightness, pain and other discomfort in the neck, as well as satisfaction with social adaptation and cosmetic incisions. The recurrence status was assessed for 1 year in both groups of patients. A questionnaire survey was conducted to assess patient acceptance of the two surgical approaches. The economic characteristics (cost-effectiveness and cost-utility) of the different approaches in our region were evaluated comprehensively. Results: The length of the incision, drainage tube carrying time and hospitalization duration were greater in the experimental group than in the control group (P < 0.05). The differences in complication rate, intraoperative bleeding volume, 24-h postoperative pain index and recurrence rate were not statistically significant between the two groups (P > 0.05). Neck discomfort was greater in the control group, and the difference was statistically significant at the 3-month postoperative follow-up (P < 0.05). The differences at the 6- and 12-month postoperative follow-ups were not statistically significant (P > 0.05). However, mild discomfort was significantly more common in the experimental group (63.33% > 36.67%, 80% > 53.33%, P < 0.05). The experimental group had better social adaptability, greater total medical costs, and better overall patient medical satisfaction than did the control group (P < 0.05). The acceptance of TAWISL was greater than that of COACAS (P < 0.05). Conclusion: Compared with COACLAS, TAWISES is safe and effective and better meets the cosmetic, psychological and social adaptation needs of patients. TAWISES is also more cost effective and can be better utilized for the population in our region, filling the gap in surgical modalities for thyroid cancer in in our region. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. 10% to 15% of individuals show familial clustering with three or more affected members, but the factors underlying this risk are unknown. In a group of recently studied individuals with POT1 pathogenic variants and ultra-long telomere length, PTC was the second most common solid tumor. We tested whether variants in POT1 and four other telomere-maintenance genes associated with familial cancer underlie PTC susceptibility. Among 470 individuals, we identified pathogenic or likely pathogenic variants in three genes encoding telomere-binding proteins: POT1 , TINF2 , and ACD. They were found in 4.5% and 1.5% of familial and unselected cases, respectively. Individuals harboring these variants had ultra-long telomere length, and 15 of 18 (83%) developed other cancers, of which melanoma, lymphoma, and sarcoma were most common. Among individuals with PTC and melanoma, 22% carried a deleterious germline variant, suggesting that a long telomere syndrome might be clinically recognizable. Successive generations had longer telomere length than their parents and, at times, developed more cancers at younger ages. Tumor sequencing identified a single oncogenic driver, BRAF p.Val600Glu, in 10 of 10 tumors studied, but no telomere-maintenance mechanism, including at the TERT promoter. These data identify a syndromic subset of PTCs with locus heterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations. DeBoy et al. identify telomere-lengthening variants in genes encoding three telomere-binding proteins as monogenic risk factors for papillary thyroid cancers, the most common of endocrine malignancies. Eighty-three percent of individuals had second cancers, of which melanoma, sarcoma, and lymphoid malignancies were most common. [ABSTRACT FROM AUTHOR]

The synchronous malignant melanoma of the neck and papillary thyroid cancer is rare but severe condition. Here, we describe the case of a patient with papillary thyroid cancer and melanoma invasivum cutis. A 49-year-old man had a change on the neck at the last 3–4 months that he accidentally noticed. He had hoarse voice, was afebrile, did not sweat more than usual and feel exhausted, without rash or itching. MR examination of the neck and upper mediastinum before the surgery indicated a hyperintense focal change in the left thyroid gland which dimensions was 19·15mm and several hyperintense inhomogeneous lymph glands of the jugular chain, on the both sides, with different sizes. On the basis of the conducted analyzes, in addition to total thyroidectomy, two-sided functional dissection of the lymph nodes of the neck was performed. The pathohistological diagnosis of the left lobus was: Carcinoma papillary glandulae thyreoideae invasivum (G-I, nG-I, pT2, Lx, Vo). CT of head, neck and thorax were made, where it was noticed that the CT of the head and lungs were normal. PET/CT findings indicated that there was no rest or recurrence of the tumor. The message from this case report is that when diagnosing and treating thyroid cancer, the observed changes in the neck lymph nodes also indicate cancers of non-thyroid pathology such as malignant melanoma. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. Objectives: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). Methods: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. Results: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method Conclusion: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers. [ABSTRACT FROM AUTHOR]

The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject. [ABSTRACT FROM AUTHOR]

Purpose: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown. Methods: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays. Results: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429. Conclusion: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Thyroid cancer is the most diagnosed endocrine cancer. There are several types of thyroid cancer, which vary in aggressiveness and survival rate. Well-differentiated thyroid cancers, such as papillary and follicular thyroid cancer, are therapeutic-responsive, with high survival rates. Anaplastic thyroid cancer is undifferentiated, represents <2% of thyroid cancer cases, and is completely unresponsive to therapy, with a grim 5-year survival rate of <4%. Varying gene expression between non-cancerous and cancerous tissue may help define similarities and differences between these thyroid cancer types and, thus, help with the development of more effective therapeutic and diagnostic strategies. Long non-coding RNA molecules are identified as important cell regulators that can alter cell behavior at several different levels. The roles of several long-noncoding RNAs have been identified to characterize thyroid cancer. This review covers several long non-coding RNAs identified for their pathologic expression patterns and functions as cancer-promoting molecules. Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations. [ABSTRACT FROM AUTHOR]

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3–18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery. [ABSTRACT FROM AUTHOR]

Background: While males present with more adverse clinicopathologic features in papillary thyroid carcinoma (PTC), younger age has previously been shown to be a favorable prognostic factor. We examined the combined effect of male sex and young age on PTC outcomes. Methods: We conducted a retrospective analysis of a prospectively maintained database of thyroid cancer surgery patients (2000–2020) at a single quaternary care institution. We included papillary thyroid carcinoma cases and excluded those with prior cancer‐related thyroid surgery. We examined demographics, cancer stage, surgical outcomes, and complications by age and sex, analyzing groups below and above the age of 40 years. Results: A total of 680 patients with PTC were included. Females constituted 68% (age ≥40 years: 44% and <40 years: 24%) and males 32% (≥40 years: 24% and <40 years: 8%). A significant difference (p < 0.001) of N1 disease distribution was found between the groups. N1a metastasis was greater in patients younger than 40 regardless of sex ((M < 40 (15%), F < 40 (15%), M ≥ 40 (12%), and F ≥ 40 (9%)). While, M < 40 had greater N1b metastasis (36%) than all other groups (M ≥ 40 (28%), F < 40 (22%), and F ≥ 40 (10%)). There was no significant difference in the distribution of T stages between groups. Groups showed no differences in 30‐day outcomes, recurrence at 1 year, reoperation, mortality, nerve injury, or hypocalcemia. Conclusions: Young males with PTC face increased occurrence of nodal metastasis yet experience similar recurrence rates as their female and older counterparts. Subgroup analysis underscores the predictive role of sex and age in advanced PTC cases. [ABSTRACT FROM AUTHOR]

Background Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases. Methods A total of 1042 lymph node metastases, derived from 129 PTC patients, were reexamined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications, and the proportion of the lymph node taken up by tumor cells. Predictors for a failure to achieve a complete biochemical and structural response to treatment were determined. Results The presence of more than 5 lymph node metastases was the only independent predictor for a failure to achieve a complete response to treatment (odds ratio [OR] 3.39 [95% CI, 1.57-7.33], P <.05). Diameter nor any of the other evaluated lymph node features were significantly associated with the response to treatment. Conclusions Detailed reexamination of lymph nodes revealed that only the presence of more than 5 lymph node metastases was an independent predictor of failure to achieve a complete response to treatment. No predictive value was found for other histopathological features, including the diameter of the lymph node metastases. These findings have the potential to improve risk stratification in patients with PTC and clinically evident lymph node metastases. [ABSTRACT FROM AUTHOR]

CircRNAs have been found to participate in the progression of various tumors. In the present study, we aimed to clarify the role of hsa_circ_0092355 in papillary thyroid cancer (PTC) cell development. RT-qPCR was used to determine the expression of hsa_circ_0092355, miR-543, and PDE5A. PTC cell proliferation was ascertained via a cell colony formation assay and the CCK-8 test. Western blotting was performed to examine the expression levels of PDE5A and apoptosis-associated proteins (Bcl-2 and Bax) in PTC cells. A scratch wound assay was performed to measure the migration of PTC cells. A mouse xenograft test was performed to assess the effects of hsa_circ_0092355 in vivo. RIP and dual-luciferase reporter assays confirmed the association between miR-543 and hsa_circ_0092355 or PDE5A. Associations between miR-543, hsa_circ_0092355, and PDE5A were evaluated using Pearson's correlation coefficient. Upregulation of hsa_circ_0092355 was observed in PTC tissues. The hsa_circ_0092355 knockdown blocked the proliferation and migration of PTC cells and induced apoptosis. Moreover, hsa_circ_0092355 knockdown blocked PTC xenograft tumor growth in vivo. The miR-543 inhibitor could reverse the changes induced by hsa_circ_0092355 knockdown by hsa_circ_0092355 targeting miR-543. Furthermore, miR-543 suppresses PTC progression by downregulating PDE5A expression. Our findings suggest that the PTC tumor promoter hsa_circ_0092355 may promote carcinogenesis by controlling the miR-543/PDE5A pathway. [ABSTRACT FROM AUTHOR]

E3 ubiquitin ligase synoviolin (SYVN1) has been reported to participate in many human cancers. This study aimed to investigate SYVN1's roles and molecular pathways in papillary thyroid cancer (PTC). The functions of SYVN1 in PTC were further analyzed using gain- and loss-of-function methods and numerous investigations in cellular function and molecular biology. The findings demonstrated that the overexpression of SYVN1 markedly suppressed the proliferation, migration, and invasion of PTC cell lines (NPA87 and TPC-1). We found that SYVN1 interacted with HMGB1 and promoted its ubiquitination and degradation. In addition, SYVN1 effectively impairs cell proliferation, migration, invasion, and the formation of tumor xenografts in mice models. However, this effect may be partly reversed by overexpressing HMGB1. Thus, SYVN1 may inhibit the proliferation, migration, and invasion of PTC cells by disrupting HMGB1. Consequently, SYVN1 might be considered a promising therapeutic target for PTC. [ABSTRACT FROM AUTHOR]

Background: Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear. Methods: In the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC. Results: The data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis. Conclusion: Taken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis. [ABSTRACT FROM AUTHOR]

Background: Although papillary thyroid cancer (PTC) patients are known to have an excellent prognosis, up to 30% of patients experience disease recurrence after initial treatment. Accurately predicting disease prognosis remains a challenge given that the predictive value of several predictors remains controversial. Thus, we investigated whether machine learning (ML) approaches based on comprehensive predictors can predict the risk of structural recurrence for PTC patients. Methods: A total of 2244 patients treated with thyroid surgery and radioiodine were included. Twenty-nine perioperative variables consisting of four dimensions (demographic characteristics and comorbidities, tumor-related variables, lymph node (LN)-related variables, and metabolic and inflammatory markers) were analyzed. We applied five ML algorithms—logistic regression (LR), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and neural network (NN)—to develop the models. The area under the receiver operating characteristic (AUC-ROC) curve, calibration curve, and variable importance were used to evaluate the models’ performance. Results: During a median follow-up of 45.5 months, 179 patients (8.0%) experienced structural recurrence. The non-stimulated thyroglobulin, LN dissection, number of LNs dissected, lymph node metastasis ratio, N stage, comorbidity of hypertension, comorbidity of diabetes, body mass index, and low-density lipoprotein were used to develop the models. All models showed a greater AUC (AUC = 0.738 to 0.767) than did the ATA risk stratification (AUC = 0.620, DeLong test: P < 0.01). The SVM, XGBoost, and RF model showed greater sensitivity (0.568, 0.595, 0.676), specificity (0.903, 0.857, 0.784), accuracy (0.875, 0.835, 0.775), positive predictive value (PPV) (0.344, 0.272, 0.219), negative predictive value (NPV) (0.959, 0.959, 0.964), and F1 score (0.429, 0.373, 0.331) than did the ATA risk stratification (sensitivity = 0.432, specificity = 0.770, accuracy = 0.742, PPV = 0.144, NPV = 0.938, F1 score = 0.216). The RF model had generally consistent calibration compared with the other models. The Tg and the LNR were the top 2 important variables in all the models, the N stage was the top 5 important variables in all the models. Conclusions: The RF model achieved the expected prediction performance with generally good discrimination, calibration and interpretability in this study. This study sheds light on the potential of ML approaches for improving the accuracy of risk stratification for PTC patients. Trial registration: Retrospectively registered at (trial registration number: ChiCTR2300075574, date of registration: 2023-09-08). [ABSTRACT FROM AUTHOR]

Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAFV600E-mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4–19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2–75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ≥1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4–5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer. Clinical Trial Registration number: Japan Registry of Clinical Trials: jRCT2011200018 [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to investigate the suggested association between body mass index and aggressive histopathological subtypes of thyroid cancer. Thus, we studied 3868 patients who underwent thyroidectomy from 2020 to 2022 at four European centres. We found that overweight and obese patients with papillary thyroid carcinoma had higher rates of aggressive histopathological subtypes, bilateral, multifocal tumours, and larger nodal metastases. These findings suggest that people with higher body mass index may be at an increased risk of developing more aggressive features of thyroid cancer. Obesity's role in thyroid cancer development is still debated, as well as its association with aggressive histopathological subtypes (AHSs). To clarify the link between Body Mass Index (BMI) and AHS of differentiated thyroid carcinoma (DTC), we evaluated patients who underwent thyroidectomy for DTC from 2020 to 2022 at four European referral centres for endocrine surgery. Based on BMI, patients were classified as normal-underweight, overweight, or obese. AHSs were defined according to 2022 WHO guidelines. Among 3868 patients included, 34.5% were overweight and 19.6% obese. Histological diagnoses were: 93.6% papillary (PTC), 4.8% follicular (FTC), and 1.6% Hürthle cell (HCC) thyroid carcinoma. Obese and overweight patients with PTC had a higher rate of AHSs (p = 0.03), bilateral, multifocal tumours (p = 0.014, 0.049), and larger nodal metastases (p = 0.017). In a multivariate analysis, BMI was an independent predictor of AHS of PTC, irrespective of gender (p = 0.028). In younger patients (<55 years old) with PTC > 1 cm, BMI predicted a higher ATA risk class (p = 0.036). Overweight and obese patients with FTC had larger tumours (p = 0.036). No difference was found in terms of AHS of FTC and HCC based on BMI category. Overweight and obese patients with PTC appear to be at an increased risk for AHS and aggressive clinico-pathological characteristics. [ABSTRACT FROM AUTHOR]

To investigate the function of ten-eleven translocation 1 (TET1) and its underlying mechanism in papillary thyroid cancer (PTC). Using the RNA-Seq data based on GDC TCGA, we analyzed the gene expression pattern of TET1 in PTC. Immunohistochemistry was carried out to assess the TET1 protein level. Then, its diagnostic and prognostic functions were determined by various bioinformatics approaches. Enrichment analysis was performed to explore the potential pathways in which TET1 is mainly involved. Finally, the immune cell infiltration analysis was conducted and the association of TET1 mRNA expression with the expression levels of immune checkpoints, tumor mutation burden (TMB) score, microsatellite instability (MSI) score, and cancer stem cells (CSC) score was examined. TET1 expression was lower in PTC tissues compared with that in normal tissues (P < 0.01). Besides, TET1 had a certain value in diagnosing PTC, and low-TET1 mRNA expression led to favorable disease-specific survival (DSS) (P < 0.01). The enrichment analysis revealed autoimmune thyroid disease and cytokine-cytokine receptor interaction were the consistent pathways in which TET1 participated. TET1 was negatively correlated with the Stromal score and Immune score. The different proportions of immune cell subtypes were observed between high- and low-TET1 expression groups. Interestingly, TET1 mRNA expression was inversely related to the expression levels of immune checkpoints, and TMB, MSI, and CSC scores. TET1 might be a robust diagnostic and prognostic biomarker for PTC. TET1 affected the DSS of PTC patients possibly through the regulation of immune-related pathways and tumor immunity. [ABSTRACT FROM AUTHOR]

Background: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. Methods: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. Results: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI+-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination. [ABSTRACT FROM AUTHOR]

Objective The accurate clinical diagnosis of cervical lymph node metastasis plays an important role in the treatment of differentiated thyroid cancer (DTC). This study aimed to explore and summarize a more objective approach to detect cervical malignant lymph node metastasis of DTC via radiomics models. Methods PubMed, Web of Science, MEDLINE, EMBASE, and Cochrane databases were searched for all eligible studies. Articles using radiomics models based on ultrasound, computed tomography, or magnetic resonance imaging to assess cervical lymph node metastasis preoperatively were included. Characteristics and diagnostic accuracy measures were extracted. Bias and applicability judgments were evaluated by the revised QUADAS-2 tool. The estimates were pooled using a random-effects model. Additionally, the leave-one-out method was conducted to assess the heterogeneity. Results Twenty-nine radiomics studies with 6160 validation set patients were included in the qualitative analysis, and 11 studies with 3863 validation set patients were included in the meta-analysis. Four of them had an external independent validation set. The studies were heterogeneous, and a significant risk of bias was found in 29 studies. Meta-analysis showed that the pooled sensitivity and specificity for preoperative prediction of lymph node metastasis via US-based radiomics were 0.81 (95% CI, 0.73-0.86) and 0.87 (95% CI, 0.83-0.91), respectively. Conclusions Although radiomics-based models for cervical lymphatic metastasis in DTC have been demonstrated to have moderate diagnostic capabilities, broader data, standardized radiomics features, robust feature selection, and model exploitation are still needed in the future. Advances in knowledge The radiomics models showed great potential in detecting malignant lymph nodes in thyroid cancer. [ABSTRACT FROM AUTHOR]

Background/aim: Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer. The critical importance of circular RNA (circRNA) in a range of cancer types has been lately recognized. However, research on the functions of circRNAs in PTC has been limited thus far. Therefore, this research aimed at exploring the function and mechanism of circ-methyltransferase-like 15 (METTL15) in PTC cells. Materials and methods: Quantitative measurements of circ-METTL15, miR-200c-3p, and X-linked inhibitor of apoptosis protein (XIAP) in PTC cells were conducted using reverse transcription-quantitative polymerase chain reaction or Western blot analysis. To investigate cell growth, cell counting kit-8 and colony formation tests were employed, apoptosis was analyzed using flow cytometry, and migration and invasion were studied through Transwell assays. The targeted binding sites between miR-200c-3p and circ-METTL15 or XIAP were predicted by starBase and then verified by dual luciferase reporter assay. Results: circ-METTL15 and XIAP were upregulated in the PTC cells, while miR-200c-3p was downregulated. Downregulating circ- METTL15 or upregulating miR-200c-3p resulted in inhibited proliferation, migration, and invasion of PTC cells, while promoting apoptosis. miR-200c-3p was the downstream molecule of circ-METTL15, and XIAP was the direct target of miR-200c-3p. Forcing XIAP expression obstructed circ-METTL15 silencing to inhibit PTC cell activity. Conclusion: By coopting miR-200c-3p/XIAP, Circ-METTL15 stimulates aggressive behavior in PTC cells. [ABSTRACT FROM AUTHOR]

Purpose: To analyze risk factors for parapharyngeal (PP) and retropharyngeal (RP) metastases in papillary thyroid cancer (PTC). Methods: A matched case–control study was conducted, comprising 130 age- and sex-matched cases of PTC. Among these cases, 50 had PP/RP metastases, 50 had central and/or lateral neck lymph node metastases, and 30 showed no lymph node metastases. Preoperative thyroid function test, computed tomography images, and postoperative pathological findings were collected. Associations between cases were assessed using univariate conditional logistic regression analysis, followed by multivariate conditional logistic regression analysis, and backward stepwise selection to predict risk factors for PP/RP metastases. Results: The study found that thyroglobulin was significantly associated with the development of PP/RP metastases [136.10(16.55–312.60) vs. 27.60(10.28–55.62) vs. 8.74(6.35–21.10) P < 0.001]. Conclusions: The study concludes that thyroglobulin is a significant risk factor for PP/RP metastases in PTC. This finding emphasizes the importance of monitoring thyroglobulin levels in PTC patients to identify those at risk of developing PP/RP metastases. [ABSTRACT FROM AUTHOR]

Background: Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive. Methods: The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of β-catenin and active β-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on β-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear β-catenin signaling. Results: CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of β-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between β-catenin and β-TrCP1, consequently impeding the ubiquitination process of β-catenin and activating the nuclear β-catenin signaling. Conclusions: CDH4 induces PTC angiogenesis and metastasis via the inhibition of β-TrCP1-dependent ubiquitination of β-Catenin. [ABSTRACT FROM AUTHOR]

Objective To investigate the factors affecting the number of lymph nodes obtained by unilateral lobectomy and isthmus combined with prophylactic ipsilateral central lymph node dissection for papillary thyroid cancer, and to analyze the pattern of change so as to provide an important basis for clinical treatment of papillary thyroid cancer. Methods Retrospective analysis was performed on the clinical and pathological data of 193 patients admitted to the department of Thyroid Surgery of the First Affiliated Hospital of Jinzhou Medical University from January 2019 to January 2022 for papillary thyroid cancer who underwent unilateral glandular lobe and isthmus resection combined with prophylactic ipsilateral central lymph node dissection. The number of obtained lymph nodes was divided into a group with high number of obtained lymph nodes (n > 6) and a group with low number of obtained lymph node((n ^ 6). Univariate analysis and multivariate analysis were used to explore the factors affecting the number of obtained lymph nodes. The influence of the number of lymph nodes on the central lymph node metastasis was evaluated by correlation analysis, and the influence of the number of lymph nodes on the quality of life of patients by postoperative complications analysis. Results The number of lymph nodes obtained was positively correlated with the number of lymph node metastases in the central region (r = 0.240, P < 0.05) and the rate of lymph node metastasis (r = 0.161,P < 0.05), respectively. The number of lymph node metastases controlled remained unchanged,and the rate of lymph node metastasis decreased with the increase of the number of obtained lymph nodes (r = -0.444, P < 0.05). Univariate analysis of the number of lymph nodes between the two groups showed no significant differences in terms of sex, age, operation duration, BMI, maximum tumor diameter, multifocality, Hashimoto's thyroiditis, focal location, capsular invasion, contralateral thyroid nodule, parathyroid transplantation and BRAF gene V600E mutation (P > 0.05). There was statistical significance in the application of nano carbon between the two groups (P < 0.05). Logistic binary regression analysis showed that the combination of Hashimoto's thyroiditis and the application of carbon nanoparticles were independent influencing factors for the high number of lymph nodes obtained (P < 0.05). ROC curve analysis suggeste- 0.735, P < 0.05), and the area under the curve occupied by Hashimoto's thyroiditis was 0.584 (95%C7: 0.504 - 0.665, P < 0.05 ). In addition, there was no significant difference in the incidence of vocal cord paralysis and lymphatic leakage between the two groups (P > 0.05). Conclusions When the number of lymph nodes in the central region remained unchanged, the higher the number of lymph nodes obtained, the lower the rate of lymph node metastasis. The application of nano-carbon and patients with Hashimoto's thyroiditis could increase the number of lymph nodes obtained, and there is no significant difference in the incidence of postoperative complications between high and low number of lymph nodes obtained. [ABSTRACT FROM AUTHOR]

Simple Summary: CHK2 has functions in DNA damage repair. Germline CHEK2 mutations impair these functions, increasing the risk of PTC. The aim of this study was to determine whether CHK2 and p53 expression in patients with a germline CHEK2 mutation in tumor tissue can serve as a prognostic marker for papillary thyroid cancer (PTC), and whether copy number aberrations in CHEK2 and TP53 correlate with the course of PTC. This study included 156 patients with PTC who had been selected from a group of 1547 people previously tested for the presence of CHEK2 mutations in their peripheral blood. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes in PTC patients. Higher CHK2 expression and positive p53 together with a TP53 deletion could have potential as a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2. The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2. [ABSTRACT FROM AUTHOR]

Background: This study was performed to evaluate the differences in oral function and psychological well-being between patients with PTC after the gasless transoral endoscopic thyroidectomy vestibular approach (gasless-TOETVA) and patients with PTC after open surgery. Methods: PTC patients who underwent radical surgery from May 2021 to August 2022 were included in this study. Postoperative data on oral function and psychological well-being, including the Oral Health Impact profile-14 (OHIP-14) and State-Trait Anxiety Inventory Form Y, were collected and analyzed. Results: 212 patients were included in the analysis. Among them, 102 patients who received gasless-TOETVA were assigned to the gasless-TOETVA group, while the remaining 110 patients who underwent open surgery were categorized as the open group. Although the OHIP-14 score in the gasless-TOETVA group was higher than that of the open group from 6 months to 1 year after surgery (p = 0.012), the difference in OHIP-14 scores between the two groups disappeared 1 year after surgery (p = 0.155). There were no differences between the gasless-TOETVA group and the open group in state-anxiety scores. However, the gasless-TOETVA group had significantly lower trait-anxiety scores than the open group at all follow-up time periods. Furthermore, within the gasless-TOETVA group, patients who were more than 1 year post-surgery showed significantly increased trait-anxiety scores compared to those of patients who were less than 1 year post-surgery (Δ = 3.4; p = 0.032). In contrast, the open group showed a decreasing trend in trait-anxiety scores, but there was no statistically significant difference between patients who had surgery less than 1 year ago and those who had surgery more than 1 year ago (Δ = − 2.2; p = 0.094). Conclusion: Gasless TOETVA had a temporary impact on oral function, but it did not alleviate the state of anxiety. Furthermore, we observed a significant increase in trait-anxiety scores among PTC patients who underwent gasless-TOETVA after 1 year. [ABSTRACT FROM AUTHOR]

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression. [ABSTRACT FROM AUTHOR]

Objective To compare the American Thyroid Association (ATA) risk staging of histologically proven papillary thyroid cancer (PTC) in patients who received a presurgery cytologic result of either indeterminate thyroid nodules (ITNs, Bethesda III/IV) or suspicious for malignancy/malignant (TIR 4/5, Bethesda V/VI). Methods Clinical, ultrasonographic, cytological data from patients with histologically diagnosed PTC were retrospectively collected. Results Patients were stratified according to the preoperative fine-needle aspiration cytology into 2 groups: 51 ITNs (TIR3A/3B) and 118 suspicious/malignant (TIR 4/5). Male/female ratio, age, and presurgery TSH level were similar between the 2 groups. At ultrasound, TIR 4/5 nodules were significantly more frequently hypoechoic (P =.037), with irregular margins (P =.041), and with microcalcifications (P =.020) and were more frequently classified as high-risk according to the European Thyroid Imaging and Reporting Data System (EU-TIRADS; P =.021). At histology, the follicular PTC subtype was significantly more prevalent among ITNs while classical PTC subtype was more frequent in TIR 4/5 group (P =.002). In TIR 4/5 group, a higher rate of focal vascular invasion (P <.001) and neck lymph node metastasis (P =.028) was observed. Intermediate-risk category according to ATA was significantly more frequent in TIR 4/5 group while low-risk category was more frequently found among ITNs (P =.021), with a higher number of patients receiving radioiodine in TIR 4/5 group (P =.002). At multivariate logistic regression, having a TIR 4/5 cytology was associated with a significant risk of having a higher ATA risk classification as compared to ITN (OR 4.6 [95% CI 1.523-14.007], P =.007), independently from presurgery findings (nodule size at ultrasound, sex, age, and EU-TIRADS score). Conclusions Papillary thyroid cancers recorded among ITNs are likely less aggressive and are generally assessed as at lower risk according to ATA classification. [ABSTRACT FROM AUTHOR]

Aldosterone (Aldo) exerts its action through binding with the mineralocorticoid receptor (MR). Clinically, a link between primary aldosteronism (PA) and thyroid diseases has been hypothesised. However, the presence and activity of MR on the thyroid have not yet been demonstrated. We investigated the gene/protein expression and activation of MR in primary thyroid cell cultures (normal rat thyroid [FRTL-5] and human papillary thyroid cancer [PTC] cell lines, BCPAP and K1) through qRT-PCR analysis, immunofluorescence, and confocal microscopy. We also studied the effects of Aldo on thyroid-specific and inflammation genes in vitro. Paired human normal and neoplastic thyroid tissues were also studied. We demonstrated both gene and protein expression and activation of MR in normal rat thyroid and human PTC lines. Incubation with Aldo induced an acute increase in IL-6 expression in both the FRTL-5 and BCPAP lines, which was antagonised by spironolactone, and an acute and late upregulation of thyroid-specific genes in FRTL-5. MR was also expressed at both gene and protein levels in normal human thyroid tissues and in PTC, with a progressive decline during neoplastic tumourigenesis, particularly in more aggressive histotypes. We present the first evidence of MR gene and protein expression in both normal and pathological thyroid cells and tissues. We have shown that MR is present and functionally activated in thyroid tissue. Binding of Aldo to MR induces the expression of inflammatory and thyroid-specific genes, and the thyroid may thus be considered a novel mineralocorticoid target tissue. [ABSTRACT FROM AUTHOR]

Introduction: Mutations of CHEK2 are usually inherited and have been implicated in breast cancers, colorectal cancers, thyroid cancers, kidney cancers, and prostate cancers. The CHEK2 gene codes for checkpoint kinase 2 protein which is an effector in the ATM-CHEK2-p53 pathway and responds to DNA double-strand breaks. Case Presentation: We describe a unique case of a 29-year-old Canadian female who presented with synchronous papillary thyroid carcinoma and rectal adenocarcinoma who was subsequently found to have a sporadic CHEK2 (checkpoint kinase 2) mutation. She presented with an 8-month history of bright red blood per rectum and saw two different physicians who diagnosed hemorrhoids and possible rectal ulcers, respectively. When the symptoms continued, the patient pursued a colonoscopy exam which found a large rectal tumor. Subsequent clinical staging diagnosed a rectal adenocarcinoma and a synchronous papillary thyroid carcinoma. Due to her synchronous tumors, a genetic panel was performed, which revealed a low-risk CHEK2 mutation. Our patient had a full response to neoadjuvant brachytherapy of the rectum and surgical treatment of her cancers. Conclusion: This is the first case report, to our knowledge, of a patient with a CHEK2 mutation who presented with synchronous papillary thyroid carcinoma and invasive colonic adenocarcinoma. The incidence of colorectal cancers and papillary thyroid cancers in those under 30 with no family history is very low, which signifies the rarity of their simultaneous occurrence at such a young age. [ABSTRACT FROM AUTHOR]

Background Regarding papillary thyroid cancer, comparisons between lobectomy (LT) and total thyroidectomy (TT) have not addressed major risks to reliable conclusions drawn from observational data. This research aimed to evaluate the survival rate following thyroidectomy (TT) and LT for papillary thyroid carcinoma. Methods A total of 155 patients with papillary thyroid cancer who had LT or TT at Menoufia University Hospitals between January 2018 and April 2023 were included in this retrospective cohort analysis. Overall survival was the main result, which was assessed using inverse probability weighting on the propensity score and flexible parametric survival models. Results Of the patients receiving treatment, 78% were female and the median age was 48 (range: 37-59). There were no statistically significant differences in the 5-year overall survival between individuals who underwent a complete thyroidectomy or LT. Furthermore, we did not find any statistically significant variation in survival by subgroups, such as age (<65 or ≥65), tumor size (<4cm or ≥4 cm), or projected risk of death. Conclusion Based on our data, TT, independent of tumor size, patient age, or overall risk of mortality, is unlikely to provide a survival benefit over lobectomy. [ABSTRACT FROM AUTHOR]

Background Leptin is a neuroendocrine hormone produced from adipose tissue with many vital functions. There is a well-known association between leptin and papillary thyroid cancer (PTC). Preoperative prediction of lymph node metastasis is one of the interesting topics in PTC. This study aimed to determine whether the serum leptin peptide is a significant predictor marker for node metastasis in cases with PTC. Patients and methods This is a prospective comparative study which was conducted at Ain Shams University Hospitals and El-Sheikh Zayed specialized hospital between January 2021 and January 2023. Forty patients with PTC were enrolled in this study and according to postoperative histopathology, we divided them into two groups: group A, 24 cases, those with pathological negative node and group B, 16 cases, those with pathological positive node. Results We had no statistically significant difference in the preoperative demographics data between both groups. Postoperatively, the median serum leptin level and percentage of leptin decrease were significantly higher in in group B. Multivariate logistic regression analysis showed that preoperative serum leptin level, thyroid imaging reporting and data system, multifocality, extra thyroid extension, and size of dominant nodule were significant predictors for node metastasis. There was a significant negative correlation between leptin level and age, while there was a significant positive correlation between leptin level and lymph node metastasis. Conclusion Preoperative serum leptin level is considered a significant predictor marker for lymph node metastasis in PTC. [ABSTRACT FROM AUTHOR]

Objectives: Precise determination of cervical lymph node metastasis (CLNM) involvement in patients with early-stage thyroid cancer is fairly significant for identifying appropriate cervical treatment options. However, it is almost impossible to directly judge lymph node metastasis based on the imaging information of early-stage thyroid cancer patients with clinically negative lymph nodes. Methods: Preoperative US images (BMUS and CDFI) of 1031 clinically node negative PTC patients definitively diagnosed on pathology from two independent hospitals were divided into training set, validation set, internal test set, and external test set. An ensemble deep learning model based on ResNet-50 was built integrating clinical variables, BMUS, and CDFI images using a bagging classifier to predict metastasis of CLN. The final ensemble model performance was compared with expert interpretation. Results: The ensemble deep convolutional neural network (DCNN) achieved high performance in predicting CLNM in the test sets examined, with area under the curve values of 0.86 (95% CI 0.78–0.94) for the internal test set and 0.77 (95% CI 0.68–0.87) for the external test set. Compared to all radiologists averaged, the ensemble DCNN model also exhibited improved performance in making predictions. For the external validation set, accuracy was 0.72 versus 0.59 (p = 0.074), sensitivity was 0.75 versus 0.58 (p = 0.039), and specificity was 0.69 versus 0.60 (p = 0.078). Conclusions: Deep learning can non-invasive predict CLNM for clinically node-negative PTC using conventional US imaging of thyroid cancer nodules and clinical variables in a multi-institutional dataset with superior accuracy, sensitivity, and specificity comparable to experts. Critical relevance statement: Deep learning efficiently predicts CLNM for clinically node-negative PTC based on US images and clinical variables in an advantageous manner. Key points: • A deep learning-based ensemble algorithm for predicting CLNM in PTC was developed. • Ultrasound AI analysis combined with clinical data has advantages in predicting CLNM. • Compared to all experts averaged, the DCNN model achieved higher test performance. [ABSTRACT FROM AUTHOR]

Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptor signaling, leading to multiple hormone resistance. Evidence on the risk of medullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking. A 43-year-old Caucasian man was referred to our endocrinology clinic for chronic hypocalcemia associated with elevated serum parathormone levels and a single cystic thyroid nodule. The patient did not show skeletal deformities, and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. The calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia. To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In the present case, a mere receptor resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitoninaemia should be carefully evaluated in PHP patients, especially in the case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic. [ABSTRACT FROM AUTHOR]

Background: Characterizing tumor microenvironment using single-cell RNA sequencing has been a promising strategy for cancer diagnosis and treatment. However, a few studies have focused on diagnosing papillary thyroid cancer (PTC) through this technology. Therefore, our study explored tumor microenvironment (TME) features and identified potential biomarkers to establish a diagnostic model for papillary thyroid cancer. Methods: The cell types were identified using the markers from the CellMarker database and published research. The CellChat package was conducted to analyze the cell–cell interaction. The SCEVAN package was used to identify malignant thyroid cells. The SCP package was used to perform multiple single-cell downstream analyses, such as GSEA analysis, enrichment analysis, pseudotime trajectory analysis, and differential expression analysis. The diagnostic model of PTC was estimated using the calibration curves, receiver operating characteristic curves, and decision curve analysis. RT-qPCR was performed to validate the expression of candidate genes in human papillary thyroid samples. Results: Eight cell types were identified in the scRNA-seq dataset by published cell markers. Extensive cell–cell interactions like FN1/ITGB1 existed in PTC tissues. We identified 26 critical genes related to PTC progression. Further, eight subgroups of PTC tumor cells were identified and exhibited high heterogeneity. The MDK/LRP1, MDK/ALK, GAS6/MERTK, and GAS6/AXL were identified as potential ligand-receptor pairs involved in the interactions between fibroblasts/endothelial cells and tumor cells. Eventually, the diagnostic model constructed by TRPC5, TENM1, NELL2, DMD, SLC35F3, and AUTS2 showed a good efficiency for distinguishing the PTC and normal tissues. Conclusions: Our study comprehensively characterized the tumor microenvironment in papillary thyroid cancer. Through combined analysis with bulk RNA-seq, six potential diagnostic biomarkers were identified and validated. The diagnostic model we constructed was a promising tool for PTC diagnosis. Our findings provide new insights into the heterogeneity of thyroid cancer and the theoretical basis for diagnosing thyroid cancer. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Intraparotid recurrence of PTC is, however, rare. Most parotid malignancies are either primary or metastatic from cancer outside the head and neck. We report a case of a 71-year-old man who had undergone lobectomy and completion thyroidectomy for PTC and presented to our clinic with an insidious intraparotid recurrence, for which he underwent a superficial parotidectomy and radioactive iodine therapy. We also present a review of the literature on similar cases. Intraparotid metastasis of PTC should be considered in the differential diagnosis of a parotid mass. [ABSTRACT FROM AUTHOR]

Aim: The aims of the study are to evaluate the predictive value of early post-operative stimulated thyroglobulin (sTg) analysis on the recurrence risk, and to define a cut-off value that is related to recurrence risk in low to intermediate risk papillary thyroid cancer (PTC). Methods: This retrospective cohort study included individuals who were diagnosed with PTC aged 18 years or older and had been operated by experienced surgeons of a tertiary university hospital between the years 2011 and 2021. The American Thyroid Association thyroid cancer guidelines version 2015 was used as the risk stratification system. Early sTg measurement obtained at 3-4 weeks after surgery when TSH >30 µIU/mL. Data was collected from the hospital database. A total of 328 patients who had post-operative early sTg values with negative anti-Tg antibodies were included. Results: The median age was 44 years. Of the 328 patients, 223 (68%) were women. The median tumor diameter was 11 mm. One hundred ninety-one patients (58.2%) had low risk and 137 (41.8%) had intermediate risk for recurrent disease. Of the 328 patients, 4.0% had recurrent disease. In multivariate Cox regression, post-operative early sTg value [OR: 1.070 (1.038-1.116), P = .000], and the pre-operative malign cytology [OR: 1.483 (1.080-2.245), P = .042] were independent risk factors for recurrence. On the ROC curve analysis, the cut-off value of early sTg was 4.1 ng/mL for those with recurrent disease. Conclusion: This study demonstrated that early sTg could predict recurrent disease in patients with low to intermediate risk PTC. A cut-off of 4.1 ng/mL was identified with a high negative predictive value. [ABSTRACT FROM AUTHOR]