Development Of Thyroid Cancer Research Articles

Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.

The study aimed to use network pharmacology research and in vitro experiments to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary thyroid carcinoma. Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis are the leading causes of death in patients with PTC. A key research focus in thyroid cancer treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including cancer, but no study has been undertaken to determine whether it can help prevent PTC. In this study, we attempted to determine through network pharmacology and in vitro experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle and invasive migration. To predict the probable targets and underlying mechanisms of silybin against PTC, a network pharmacology research was performed. In vitro experiments were conducted to further evaluate silybin's anti-cancer properties and priority targets against PTC. The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment analysis suggested that the target genes were enriched in functions and pathways related to PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks, the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1), N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint gene expression levels were positively correlated with the expression levels of the hub genes. Silybin decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations. When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked, CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were dramatically reduced, while E-cadherin expression was significantly elevated. These findings provide preliminary evidence that silybin inhibits PTC cell proliferation, metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological checkpoint gene expression levels. These studies provide a theoretical and experimental scientific basis for the potential anticancer effects of silybin on PTC.

The Underestimated Impact of Hashimoto Thyroiditis on Thyroid Papillary Carcinoma.

It is stated that Hashimoto's Thyroiditis (HT) is a risk factor for the development of Papillary Thyroid Cancer (PTC). However, the effect of HT on the coexistence of HT and PTC is still controversial. In this study, our aim is to investigate the effect of the presence of HT on clinicopathological data in patients with PTC. All 356 patients whose pathology was reported as PTC who were operated between 2015 and 2023 were included in the study. PTC patients were divided into 2 groups as those with and without HT. The effect of HT association on clinicopathological features was investigated. In 356 PTC patients, the rate of HT was 31.2%. PTC patients with HT had less multifocality (p < 0.05), more lymph node metastases (LNM) (p < 0.01) compared to PTC patients without HT. The presence of HT did not affect the bilaterality of the tumor, tumor diameter, lymphovascular invasion, or capsule invasion. While multifocality was observed less frequently in PTC patients with HT, lymph node metastasis rates were higher.

Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study

ObjectiveTo investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer.DesignScandinavian cohort study.SettingDenmark, Norway, and Sweden, 2007-21.ParticipantsPatients who started GLP1 receptor agonist...

Exploring the Link between BMI and Aggressive Histopathological Subtypes in Differentiated Thyroid Carcinoma-Insights from a Multicentre Retrospective Study.

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.

Thyroid cancer risk in women after hysterectomy: A nationwide cohort study

ObjectivesHysterectomy is commonly performed for benign uterine pathologies but there is some controversy over whether it is associated with an increased risk of thyroid cancer. This study examines the associations of hysterectomy with ovarian conservation or with bilateral salpingo-oophorectomy and thyroid cancer incidence in Taiwan. MethodsWe analyzed data from a nationwide health insurance claims database and identified 29,577 women aged ≥30 years who underwent hysterectomy with ovarian conservation or hysterectomy with bilateral salpingo-oophorectomy between 2000 and 2016. Propensity score-matching analyses were performed at ratios of 1:1 for the hysterectomy and no-hysterectomy groups, to reduce selection bias. We monitored thyroid cancer occurrence in both groups until 2017. Cox regression was used to calculate hazard ratios with 95 % confidence intervals and determine thyroid cancer risk in women who underwent hysterectomy. ResultsThe study comprised 29,577 patients who underwent any hysterectomy and 29,577 participants who did not. The mean follow-up period was 10.03 ± 4.92 years. Patients who underwent hysterectomy had higher thyroid cancer incidence (4.72 per 10,000 person-years) than those who did not (3.06 per 10,000 person-years) and a greater risk of any thyroid cancer (adjusted hazard ratio = 1.40; 95 % confidence interval = 1.08–1.82). However, there was no association between hysterectomy with bilateral salpingo-oophorectomy and thyroid cancer incidence (p > 0.05). ConclusionsOur findings suggest that women who undergo hysterectomy are at a higher risk of developing thyroid cancer than those who do not.

Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective medications for the treatment of type 2 diabetes and obesity. Pharmacological studies in rodents support an association between the use of GLP-1 RAs and the development of medullary thyroid cancer (MTC) resulting in a black box warning for these agents in patients at risk for this condition. Yet, the association between GLP-1 RAs and non-MTC remains controversial. Excessive worry about unproven thyroid cancer risk might lead to underutilizing GLP-1 RAs in patients who could otherwise experience substantial benefits. Unwarranted concerns about thyroid cancer could lead to unnecessary thyroid cancer screening and harms from overdiagnosis. Summary: The body of evidence assessing the association between GLP-1 RA use and thyroid cancer spans a wide range of methodologies, including basic and translational research investigating biological plausibility; randomized trials assessing clinical efficacy and providing the strongest evidence for causality; observational studies providing real-life outcome evaluation in larger populations but with limited evaluation of covariates or dependable outcome definitions; and pharmacovigilance studies that provide postmarketing assessments of a safety signal but do not address causality. There is biological plausibility supporting an association between GLP-1 RA and MTC in rodents, which is less clear for non-MTC in humans. Clinical evidence from randomized trials and associated meta-analysis suggest thyroid cancer as a rare event making effect estimates imprecise but without conclusive and consistent evidence of increase risk in those receiving GLP-1 RA. Observational studies at higher risk of bias also show low event rates for thyroid cancer, with effect estimates that are inconsistent among different studies. Pharmacovigilance studies consistently show a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RA. Conclusions: Evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA. Observational studies at higher risk of bias yield inconsistent results. Overall there is no conclusive evidence of elevated thyroid cancer risk. These findings can help clinicians when addressing patient's concerns about a potential yet unproven link between GLP-1 RA therapy and thyroid cancer.

Potential Role of Selected miRNAs in the Pathogenesis of Autoimmune Thyroid Diseases in Children and Adolescents.

Many epigenetic factors, including microRNAs, are involved in the process of changing gene expressions. Small non-coding RNA molecules, called miRNAs, are responsible for regulating gene translation by silencing or degrading target mRNAs. It is acknowledged that for many diseases, they may be novel diagnostic and prognostic biomarkers. Patients with autoimmune thyroid diseases are more likely to develop nodules in the thyroid tissue, and Hashimoto's thyroiditis and Graves' disease predispose patients to thyroid cancer. We evaluated the concentrations of microRNA molecules (miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p, miR-150-5p) in the blood of children with thyroid disorders. In addition, we wished to identify molecules whose change in concentration predisposes to the development of thyroid cancer. The aim of this study is to evaluate selected epigenetic elements by analyzing the levels of miR-15a-5p, miR-126-3p, miR-142-5p, miR-150-5p and miR-21-5p in the blood of pediatric patients with Graves' disease (n = 25), Hashimoto's thyroiditis (n = 26) and thyroid nodular disease (n = 20) compared to a control group of healthy children (n = 17). The study consists of groups of children and adolescents aged 10-18 years with autoimmune thyroid disease, with thyroid nodular disease compared to a control group. The miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p and miR-150-5p molecules were determined through an immunoenzymatic assay using BioVendor reagents. There is a statistically significant decrease in the expression of the miR-15a-5p in children with Graves' disease (21.61 vs. 50.22 amol/μL, p = 0.03) and in patients with thyroid nodular disease compared to controls (20.23 vs. 50.22 amol/μL, p = 0.04). Higher levels of the miR-142-5p molecule are found in patients with thyroid disease (with GD-3.8 vs. 3.14 amol/μL, p = 0.01; with HT-3.7 vs. 3.14 amol/μL, p = NS, with thyroid nodular disease-4.16 vs. 3.14 amol/μL, p = 0.04). Lower levels of miR-126-3p were noted in the GD group compared to the control group (7.09 vs. 7.24 amol/μL, p = 0.02). No statistically significant changes in the expressions of miR-150-5p and miR-21-5p molecules were observed in the study groups. 1. The overexpression of the miR-142-5p molecule occurs in children and adolescents with thyroid diseases. 2. Decreased blood levels of miR-15a-5p predispose patients to the formation of focal lesions in the thyroid gland. 3. Identifying a lower expression of the miR-126-3p molecule in the blood of children with GD requires careful follow-up for the development of focal lesions in the thyroid gland and evaluation for their potential malignancy.

Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer.

The incidence of thyroid cancer in women is 3-4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. Ingenuity pathways analysis was used to define sex-biased gene networks using data from the Cancer Genome Atlas (TCGA). Confirmatory studies were performed through the analysis of histone lysine demethylases (KDMs) expression by real-time PCR and immunostaining. In normal thyroids, 44 sex-biased genes were comparatively upregulated in male and 28 in female patients. The expressions of 37/72 (51%) sex-biased genes were affected in cancer tissues compared with normal thyroids. Gene network analyses revealed sex-specific patterns in the expressions of KDM5C, KDM5D, and KDM6A. In confirmatory studies, KDM5D mRNA and protein were detected only in males, whereas KDM5C and KDM6A were detected in samples from male and female patients. Nuclear staining with anti-KDMs was found in normal thyroids, but a loss of nuclear expression with a concomitant gain of cytoplasmic staining was observed in cancer tissues. Normal thyroids have a sex-specific molecular signature, and the development of thyroid cancer is associated with a differential expression of sex-biased genes. The sex-specific expression of KDMs, coupled with cancer-related alterations in their intracellular localization, may contribute to mechanisms underlying sex differences in thyroid tumorigenesis.

Abstract 54: Engineering chimeric antigen receptor (CAR) T cells using autoantigen binding domains for treatment of B cell malignancies with increased specificity

Abstract Introduction: Chronic inflammation often leads to cancer, and many autoimmune diseases lead to a significantly increased risk of developing cancer. Though many autoimmune diseases, like Graves’ Disease (GD), don’t have treatments that address this risk. Chimeric antigen receptor (CAR) T cells are an effective treatment for hematological cancers by eliminating all B cells, but a more targeted form of CAR T cells could eliminate specific B cell populations in B cell malignancies, including GD. Methods: To allow our CAR T cells to target specific B cell populations that cause GD, we engineered chimeric autoantigen receptors (CAAR) with epitopes of thyroid stimulating hormone receptor (TSHR) as the binding domain. This acts as bait for the anti-TSHR B cells. Jurkat T cells were lentivirally transduced with these CAAR plasmids. Anti-TSHR B cell lines were engineered by transducing Nalm6 cells with lentivirus for anti-TSHR B cell receptors. Cytotoxicity assays were performed on primary human TSHR CAAR T cells incubated with the anti-TSHR B cell lines. Cytokine production, proliferation, and cytotoxicity assays were performed on these coincubated cells to determine the efficacy of our TSHR CAAR T cells. Results: Two of the three Jurkat TSHR CAAR T cells showed significant binding to anti-TSHR antibodies (TRAbs). They also showed significant activation, measured by CD69 expression, when incubated with plate bound TRAbs, but not soluble TRAbs. The B cell lines were validated by binding to TSHR. The primary TSHR CAAR T cells showed significantly increased proliferation and production of TNF, IFN-y, and IL-2, when compared with controls. The TSHR CAAR T cells also had significant cytotoxic action against the anti-TSHR B cell lines, but not Nalm6 B cells. The cytotoxic function was comparable to our CD19 CAR T cell with the same activation domains, though it demonstrated specificity to only anti-TSHR B cells. Conclusion: TSHR CAAR T cells are a potentially curative treatment for GD that will stop chronic inflammation and could reduce GD patient’s risk of developing thyroid cancer. This is also an important development in CAR T cell therapies that allows for specific targeting of certain B cell populations. Citation Format: Abiagil Cheever, Hunter Lindsay, MacKenzie Hansen, Chloe Kang, K. Scott Weber, Kim O'Neill. Engineering chimeric antigen receptor (CAR) T cells using autoantigen binding domains for treatment of B cell malignancies with increased specificity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 54.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study

BackgroundThe 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.MethodsThis 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.ResultsThere 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. <LOD, OR = 1.61, 95% CI, 1.09, 2.38; p for trend = 0.05) and significantly decreased risk of follicular variant PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 0.38, 95% CI, 0.16, 0.91; p for trend = 0.04). Further stratified by sex, risk of classical PTC was higher for females (third tertile above LOD vs. <LOD, OR = 2.23, 95% CI: 1.23, 4.06; p-trend = 0.02) than for males (OR = 1.22, 95%CI: 0.72–2.08; p-trend = 0.56), though the test for interaction by sex was not statistically significant (p-interaction = 0.30). Similarly, β-hexachlorocyclohexane (β-HCCH) was associated with a higher risk for classical PTC for women with concentrations ≥LOD versus <LOD (OR = 1.76, 95% CI: 1.07, 2.89), while the effects were null for men. There were no consistent trends when stratified by race or birth year. ConclusionsThe U.S. Environmental Protection Agency has classified HCB and other OCPs we studied here as probable human carcinogens. Our findings of increased risks for classical PTC associated with increased concentrations of HCB and β-HCCH, which were stronger among females, should be replicated in future studies of other populations.

Adiponectin Inhibits the Progression of Obesity-Associated Papillary Thyroid Carcinoma Through Autophagy.

Obesity is a risk factor for the development of papillary thyroid cancer (PTC). However, the molecular mechanisms by which obesity promotes PTC are unclear. This study aims to identify adipokines that are linked to PTC progression. An adipokine antibody array was used to determine the serum levels of 40 adipokines in normal-weight and obese PTC patients. Enzyme-linked immunosorbent assay was used to determine the serum levels of adiponectin. Recombinant human adiponectin was produced by human adipose-derived stem cells and used to treat PTC cells. Cell proliferation and migration were evaluated using the CCK8 and Transwell assays. Bioinformatics analysis was used to predict mechanisms by which adiponectin affects PTC. Adipokines differentially expressed between normal-weight and obese patients showed a gender-dependent pattern. Obese PTC patients had a significantly lower serum adiponectin level than normal-weight patients, especially in female individuals. Adiponectin levels were negatively correlated with aggressive features of PTC, including tumor diameter > 1 cm, extrathyroidal extension, and lymph node metastasis. Recombinant human adiponectin inhibited the proliferation and migration of human PTC cells in vitro. Bioinformatics analysis identified adiponectin receptor 2 (ADIPOR2) and the autophagy pathway as possible mediators of adiponectin function in TC. In vitro experiments confirmed that adiponectin activated autophagy in PTC cells. These findings shed new lights into the role and mechanisms of adiponectin in TC pathogenesis. Adiponectin is involved in development of obesity-related PTC. Adiponectin can directly inhibit thyroid cancer growth and metastasis through the autophagy pathway.

Modifiable risk factors for thyroid cancer: lifestyle and residence environment.

In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer.

LncRNAs associated with lymph node metastasis in thyroid cancer based on TCGA database

ObjectiveLong non-coding RNA (lncRNA), especially RNA associated with lymph node metastasis, plays an important role in the development of cancer. Identifying metastasis related lncRNAs and exploring their clinical significance can guide the treatment and prognosis of thyroid cancer patients. MethodsRNA expression and clinical data of thyroid cancer was derived from The Cancer Genome Atlas (TCGA) database, while the survival data was obtained from the ULCAN database. R language and SPSS software were used to analyze the correlation between lncRNA and lymph node metastasis of thyroid cancer and the lncRNAs associated with lymph node metastasis were screened. Result10 lncRNAs showed significant differential expression in thyroid cancer with and without lymph node metastasis. Four lncRNAs (LRRC52-AS1, AP002358.1, AC004847.1, and AC254633.1) were overexpressed in metastatic thyroid cancer, while six lncRNAs (SLC26A4-AS1, LINC01886, LINC01789, AF131216.3, AC062015.1, and AL031710.1) were underexpressed. The expression levels of these lncRNAs were associated with the clinical staging of tumors. Cox regression analysis further showed that elevated expression levels of AP002358.1 and LRRC52-AS1 were associated with poor prognosis in patients with thyroid cancer. In addition, analysis of the UALCAN database indicated that these two lncRNAs were significantly overexpressed in thyroid cancer compared to other cancers, and the expression levels of AF131216.3 and AL031710.1 were associated with progression-free survival in thyroid cancer patients. ConclusionThese lncRNAs may play crucial roles in the development and progression of thyroid cancer and could serve as potential markers for predicting tumor metastasis, clinical stage, and patient prognosis.

GSG2 promotes thyroid cancer via stabilizing AURKB and activating AKT pathway.

Thyroid cancer stands out as the most prevalent endocrine cancer, with its incidence on a global rise. While numerous studies have delved into the roles of GSG2 in the progression of various malignancies, its involvement in thyroid cancer remains relatively unexplored. Therefore, this study was initiated to assess the functional importance of GSG2 in human thyroid cancer development. Our findings revealed a notable upregulation of GSG2 in both thyroid cancer tissues and cell lines, demonstrating a significant correlation with the pathological stage and patients' prognosis. Depletion of GSG2 in thyroid cancer cells resulted in suppressed malignant cell development and inhibited tumor outgrowth. Crucially, our investigation identified AURKB as a downstream gene of GSG2. GSG2 exhibited its regulatory role by stabilizing AURKB, countering SMURF1-mediated ubiquitination of AURKB. Furthermore, overexpressing AURKB restored the functional consequences of GSG2 depletion in thyroid cancer cells. Additionally, we proposed the involvement of the AKT pathway in GSG2-mediated regulation of thyroid cancer. Intriguingly, the reversal of cell phenotype alterations in GSG2-depleted cells following an AKT activator underscored the potential link between GSG2 and the AKT pathway. At the molecular level, GSG2 knockdown downregulated p-AKT, an effect partially restored after AKT activator treatment. In summary, our study concluded that GSG2 played a pivotal role in thyroid carcinogenesis, underscoring its potential as a therapeutic target for thyroid cancer.

Causal relationship of genetically predicted gut microbiota with thyroid cancer: a bidirectional two-sample mendelian randomization study.

Previous investigations have demonstrated a correlation between the composition of gut microbiota and the development of thyroid cancer (TC). Nonetheless, there was no consensus on the causal effect of gut microbiota composition on TC risk. Therefore, the present study aimed to perform a bidirectional two-sample Mendelian randomization (MR) analysis to explore potential causal associations between gut microbiota and TC risk. Utilizing data from the MiBioGen consortium's genome-wide association studies (GWAS) meta-analysis involving a sample size of 18,340, we identified instrumental variables for 211 gut microbiota taxa. The summary statistics for TC was from relevant large-scale GWAS conducted by the FinnGen consortium. In the first stage, the Inverse-variance weighted (IVW) method was used as the primary estimate method, and the stability of estimations was tested by a battery of sensitivity analyses. In the second stage, a reverse MR analysis was applied to determine whether reverse causality existed. According to the IVW method, we identified 9 genetically predicted gut microbiota that were causally correlated with TC risk. Among them, we observed a positive causal effect of Family Christensenellaceae (OR = 1.664, 95% CI: 1.103-2.511, P = 0.015), Family Victivallaceae (OR = 1.268, 95% CI: 1.009-1.594, P = 0.042), Genus Methanobrevibacter (OR = 1.505, 95% CI: 1.049-2.159, P = 0.027), Genus Ruminococcus2 (OR = 1.846, 95% CI: 1.261-2.704, P = 0.002), Genus Subdoligranulum (OR = 1.907, 95% CI: 1.165-3.121, P = 0.010), Phylum Verrucomicrobia (OR = 1.309, 95% CI: 1.027-1.668, P = 0.029) on TC risk, while Class Betaproteobacteria (OR = 0.522, 95% CI: 0.310-0.879, P = 0.015), Family Family XI (OR = 0.753, 95% CI: 0.577-0.983, P = 0.037), Genus Sutterella (OR = 0.596, 95% CI: 0.381-0.933, P = 0.024) might be correlated with a decreased risk of TC. Subsequently, various sensitivity analyses indicated no heterogeneity, directional pleiotropy or outliers. In addition, reverse analysis demonstrated a negative causal effect of TC risk on the abundance of the gut microbiota (Genus Ruminococcus2, OR = 0.947, 95% CI: 0.907-0.989, P = 0.014). Genetic evidence suggested that bidirectional causal associations of specific bacteria taxa and the risk of TC, highlighting the association of the "gut-thyroid" axis. Further exploration of the potential microbiota-related mechanisms might have profound implications for public health in terms of the early prevention and treatment of TC.

The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.

The effect of micronutrients on thyroid cancer has been studied in observational studies, however, the cause of relationships has not yet been determined. Thyroid cancer was the subject of a Mendelian randomization (MR) analysis of micronutrients. Aimed to determine whether micronutrient intake has a causal impact on the chance of developing thyroid cancer. We used a Mendelian randomization (MR) analysis with two samples. Our circulation levels of Cu, Ir, Zn, Ca, VD, and VC were reflected by genetic variations reported from GWAS in individuals of European ancestry. For the GWAS outcome of thyroid cancer. Sensitivity studies that included MR-Egger, weighted median/mode tests, and a more open selection of variations at a genome-wide sub-significant threshold were added to our inverse-variance weighted (IVW) MR study. Using the IVW approach, we did not find evidence that any of the micronutrients to thyroid cancer (Cu: odds ratio [OR = 0.88, p = 0.41]; Zn: odds ratio [OR = 0.87, p = 0.40]; Ir: odds ratio [OR = 1.18, p = 0.39]; Ca: odds ratio [OR = 1.12, p = 0.43]; VC: odds ratio [OR = 0.95, p = 0.22]; VD: odds ratio [OR = 0.89, p = 0.04]). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. This study does not provide evidence that supplementation with micronutrients including Cu, Ir, Zn, Ca, VD, and VC can prevent thyroid cancer.

Sciellin promotes the development and progression of thyroid cancer through the JAK2/STAT3signaling pathway.

Thyroid cancer (TC) is one of the most common endocrine tumors worldwide. Sciellin (SCEL) is involved in various disease processes, including burn wound healing and neutrophil extracellular traps (NETs); it is highly expressed in TC. However, its biological impact on TC and related mechanisms remain unclear. This study aimed to investigate the effect of SCEL on the function of human TC cell lines B-CPAP and OCUT-2C (cancer cell lines with BRAF V600E mutations). Analyses of data sets and clinical samples revealed enhanced expression of SCEL in TC than in adjacent normal tissue. SCEL knockout suppresses proliferation and cell cycle progression in TC cells, and these results were reversed by the upregulated SCEL expression in TC. SCEL knockout inhibited tumor development in xenograft mouse models. Western blot (WB) demonstrated that the expression of p-JAK2 and p-STAT3 was reduced in SCEL-knockdown TC. These results suggest that SCEL plays a key role in TC progression through the JAK2-STAT3 pathway. Therefore, SCEL can be considered a potential diagnostic biomarker and therapeutic target for TC.

Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

Establishment and Characterization of Amitrole-Induced Mouse Thyroid Adenomatous Nodule-Derived Cell Lines.

Background: Thyroid cancer cell lines have been of great value for the study of thyroid cancer. However, the availability of benign thyroid adenoma cell lines is limited. Methods: Cell lines were established from thyroid adenomatous nodules that developed in mice treated with the goitrogen amitrole. Expression of epithelial, mesenchymal, and thyroid markers of these established cell lines was determined, and the effect of lentivirus-transduced overexpression of NKX2-1, a master regulator of thyroid development, on the thyroid marker expression was examined. Signal transduction and cell proliferation were evaluated after treatment with insulin-like growth factor-I (IGF-I) and the selective IGF-I receptor (IGF-IR) inhibitor NVP-ADW742. Xenograft studies were performed to examine tumorigenicity of the cells in mice. Whole-genome sequencing (WGS) was used to comprehensively determine the genetic mutations in the established two cell lines. Results: Five mouse thyroid adenomatous nodules-derived cell lines named CAT (cells from amitrole-treated thyroids) were established. Among these, two cell lines, CAT458/458s (CAT458s: a subline of CAT458) and CAT459, were found to be positive for epithelial markers and negative for a mesenchymal marker. NKX2-1-positive CAT459 cells showed higher messenger RNA (mRNA) expression of some thyroid differentiation markers than NKX2-1-negative CAT458s cells, and NKX2-1 overexpression increased and/or induced their expression. IGF-I signaling was transduced in thyrotropin receptor (Tshr)-negative CAT458s and 459 cells, and NVP-ADW742 suppressed their proliferation. No tumors developed in mice after subcutaneous injection of CAT458s or 459 cells. The WGS analysis revealed the presence of missense mutations in the tumor suppressor genes such as Polk (encoding DNA polymerase kappa) and Tgfb1 (encoding transforming growth factor beta 1), while no mutations were found in the prominent thyroid cancer-related genes Braf, Trp53 (encoding p53), and Tert (encoding telomerase reverse transcriptase). Conclusions: Two mouse thyroid adenomatous nodule-derived cell lines with different thyroid differentiation marker expression were established. NKX2-1 induced partial differentiation of these cell lines. They lacked tumorigenicity and prominent gene mutations involved in thyroid cancer development, while missense mutations were found in some tumor suppressors as revealed by WGS. The CAT458s and 459 provide a new tool to further clarify the process of thyroid multistep carcinogenesis and differentiation.

Global scientific trends on thyroid disease in early 21st century: a bibliometric and visualized analysis.

Bibliometrics has been used to analyze the literature in the field of thyroid disease studies in the early 21st century, indicating the changes in current international study trends. In this study, a bibliometric analysis of data retrieved from the Web of Science (WoS) database was conducted, and the publication trends and thematic evolution in the field of thyroid disease research from January 1, 2000, to November 16, 2022, were analyzed. A total of 69283 articles related to thyroid diseases were evaluated for their characteristics, including annual publication volume, countries, journals, institutions, authors, keywords, and references. VOSviewer was utilized to perform the analysis of co-authorship, co-citation, co-occurrence and descriptive. The annual publication volume of thyroid disease research literature showed a fluctuating upward trend from 2000 to 2021, exceeding 5,000 articles for the first time in 2021. The United States (16120 counts, 678255 cities) ranks first in terms of publication volume and citation. Thyroid (n=3201) and Journal of Clinical Endocrinology&Metabolism (n=140399) are the most prolific and cited journals, respectively. The organization with the highest publication volume and citation frequency is Harvard University (1011 counts, 59429 cities), Miyauchi Akira (n=422), Schlumberger, and Martin (n=24839) possess the highest publication volume and citation frequency, respectively. Co-occurrence analysis of 307 keywords with frequencies of more than 20 resulted in 6 clusters (1): Thyroid dysfunction and diseases (2); mechanism of occurrence and development of thyroid cancer (3); autoimmune thyroiditis (4); scope and postoperative management of thyroid surgery (5); fine needle aspiration of thyroid nodules (6); radioactive iodine therapy for thyroid cancer. Active monitoring, thermal ablation, Lenvatinib, and long noncoding RNA refer to the latest keywords. Discussing the six clusters helps scholars to determine the scope and direction of studies. Over the past two decades, the literature related to thyroid diseases has increased year by year, with closer collaboration between countries, institutions, and authors. In this study, the global trends, research hotspots, emerging subjects, and basic knowledge of literature related to thyroid diseases were respectively elucidated, which will facilitate researchers in this field to seek better development.