thyroid neoplasms

甲状腺肿瘤
  • 文章类型: Journal Article
    为了更准确地诊断和治疗不同亚型甲状腺癌,我们构建了与THCA亚型碘代谢相关的诊断模型.THCA表达谱,相应的临床病理信息,和单细胞RNA-seq从TCGA和GEO数据库下载。通过GSVA获得与甲状腺分化评分相关的基因。通过逻辑分析,最后构建了诊断模型。DCA曲线,ROC曲线,机器学习,采用K-M分析验证模型的准确性。qRT-PCR用于验证hub基因的体外表达。不同TDS和THCA亚型之间有104个交叉基因。最后,5个基因(ABAT,获得了可以独立预测TDS亚群的CHEK1,GPX3,NME5和PRKCQ),并构建了诊断模型。ROC,DCA,和RCS曲线表明该模型具有准确的预测能力。K-M和亚组分析结果表明,在THCA患者中,低模型评分与低PFI密切相关。模型评分与T细胞滤泡辅助细胞呈显著负相关。此外,诊断模型与免疫评分呈显著负相关.最后,qRT-PCR结果与生物信息学结果一致。该诊断模型对THCA患者具有良好的诊断和预后价值,可作为THCA患者的独立预后指标。
    To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.
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  • 文章类型: Journal Article
    间变性甲状腺癌(ATC)是侵袭性最强的甲状腺癌,预后差,转移复发的可能性高。癌细胞的长期存活取决于它们在有利环境中定居的能力。癌细胞与肿瘤微环境中的其他细胞相互作用,形成“土壤”,并通过形成极其复杂的肿瘤生态系统使其适合细胞生长。细胞外基质(ECM)是肿瘤生态系统的重要组成部分,其生物学和力学变化强烈影响肿瘤的侵袭,转移,免疫逃逸和耐药性。与正常组织相比,生物过程,如胶原蛋白合成和ECM信号,在ATC组织中被显著激活。然而,ATC如何触发ECM特性的变化及其与ECM的相互作用仍然缺乏表征。因此,深入研究ATC中ECM信号异常激活的调节机制对于通过破坏癌细胞赖以生存的“土壤”来实现发挥抗肿瘤作用的治疗目标非常重要。在这项研究中,我们揭示了ATC进展中ECM信号的异常活化状态,并试图揭示ATC中ECM成分的潜在作用机制,目的是为ATC治疗提供新的药物靶点。
    Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer, and it has a poor prognosis and high probability of metastatic recurrence. The long-term survival of cancer cells depends on their ability to settle in a favorable environment. Cancer cells interact with other cells in the tumor microenvironment to shape the \"soil\" and make it suitable for cell growth by forming an extremely complex tumor ecosystem. The extracellular matrix (ECM) is an essential component of the tumor ecosystem, and its biological and mechanical changes strongly affect tumor invasion, metastasis, immune escape and drug resistance. Compared to normal tissues, biological processes, such as collagen synthesis and ECM signaling, are significantly activated in ATC tissues. However, how ATC triggers changes in the properties of the ECM and its interaction with the ECM remain poorly characterized. Therefore, an in-depth study of the regulatory mechanism of the abnormal activation of ECM signaling in ATC is highly important for achieving the therapeutic goal of exerting antitumor effects by destroying the \"soil\" in which cancer cells depend for survival. In this research, we revealed the aberrant activation state of ECM signaling in ATC progression and attempted to uncover the potential mechanism of action of ECM components in ATC, with the aim of providing new drug targets for ATC therapy.
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  • 文章类型: Journal Article
    为了评估可行性,功效,微波消融治疗滤泡性甲状腺肿瘤和可疑滤泡性甲状腺肿瘤的安全性。
    在这项回顾性研究中,总结2016年12月至2024年1月微波消融治疗滤泡性肿瘤的患者资料.结节大小的变化,volume,技术成功率,疾病进展,完整的肿瘤分辨率,甲状腺功能,并对消融后的并发症进行了评估。
    74名患者(15名男性,包括59名女性;平均年龄46.3±15.2岁)的滤泡性肿瘤。在13个月的中位随访时间内,实现了完全消融,给出100%的技术成功率。在消融后的第一个月,结节最大直径无明显变化(p=0.287)。从第三个月开始,最大直径和体积均显着降低(全部p<0.005)。体积减少率在1个月和3个月保持稳定(分别为p=0.389和0.06),但此后显着增加(全部p<0.005)。到24个月,中值最大直径从2.3厘米减少到0厘米,实现100%的中位体积减少率。20.3%(15/74)的结节完全消失。2.7%的病例出现局部复发(2/74),无转移或肿瘤相关死亡报告。治疗后甲状腺功能无变化(p>0.05)。并发症和副作用发生率分别为8.1%和4.1%,分别。
    初步研究结果表明,微波消融治疗滤泡性肿瘤是一种安全有效的治疗方法,疾病进展和并发症发生率低,同时保持甲状腺功能。
    UNASSIGNED: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms.
    UNASSIGNED: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated.
    UNASSIGNED: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively.
    UNASSIGNED: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.
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  • 文章类型: Journal Article
    甲状腺癌是最常见的内分泌相关恶性肿瘤,其中间变性甲状腺癌(ATC)是最致命的亚型。蛋白质的合成是活跃的,以满足ATC肿瘤的快速生长,但是调节蛋白质合成的机制仍然未知。我们的研究表明,动粒蛋白NUF2在蛋白质合成中起着至关重要的作用,并推动了ATC的发展。甲状腺癌患者的预后与NUF2高表达呈正相关。NUF2在ATC细胞中的耗竭显著抑制细胞增殖和诱导细胞凋亡,而NUF2的过表达促进ATC细胞活力和集落形成。NUF2的缺失显著抑制了体内ATC的生长和转移。值得注意的是,NUF2的敲减通过降低启动子处的H3K4me3的丰度来表观遗传抑制镁转运蛋白的表达,从而降低细胞内Mg2+浓度。此外,我们发现NUF2或镁转运体的缺失显著抑制了PI3K/Akt/mTOR通路介导的蛋白质合成.总之,NUF2通过维持细胞内Mg2的稳态,作为蛋白质合成的新兴调节剂,这最终推动了ATC的发展。
    Thyroid cancer is the most frequently observed endocrine-related malignancy among which anaplastic thyroid cancer (ATC) is the most fatal subtype. The synthesis of protein is active to satisfy the rapid growth of ATC tumor, but the mechanisms regulating protein synthesis are still unknown. Our research revealed that kinetochore protein NUF2 played an essential role in protein synthesis and drove the progression of ATC. The prognosis of patients with thyroid carcinoma was positively correlated with high NUF2 expression. Depletion of NUF2 in ATC cells notably inhibited the proliferation and induced apoptosis, while overexpression of NUF2 facilitated ATC cell viability and colony formation. Deletion of NUF2 significantly suppressed the growth and metastasis of ATC in vivo. Notably, knockdown of NUF2 epigenetically inhibited the expression of magnesium transporters through reducing the abundance of H3K4me3 at promoters, thereby reduced intracellular Mg2+ concentration. Furthermore, we found the deletion of NUF2 or magnesium transporters significantly inhibited the protein synthesis mediated by the PI3K/Akt/mTOR pathway. In conclusion, NUF2 functions as an emerging regulator for protein synthesis by maintaining the homeostasis of intracellular Mg2+, which finally drives ATC progression.
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  • 文章类型: Journal Article
    为分化型甲状腺癌(DTC)患者切除和放射性碘(RAI)治疗后的左旋甲状腺素(L-T4)剂量选择,使用机器学习建立预测模型,并前瞻性地验证两个机构的模型的准确性。
    本回顾性研究共纳入266例甲状腺切除术后接受RAI治疗并达到促甲状腺激素(TSH)目标水平的DTC患者。收集可能影响L-T4剂量的16个临床和生化特征;使用机器学习随机森林方法选择与L-T4剂量相关的显著特征,总共建立了8个回归模型来评估其在预测RAI治疗后的L-T4剂量方面的表现;通过两中心前瞻性研究(n=263)验证了最佳模型。
    选择了六个重要的临床和生化特征,包括体表面积(BSA),体重,血红蛋白(HB),高度,体重指数(BMI),和年龄。交叉验证表明,在建立的8个模型中,支持向量回归(SVR)模型对L-T4剂量的预测准确率最高(53.4%)。在双中心前瞻性验证研究中,共纳入263例患者.基于构建的SVR模型的TSH靶向率显着高于基于经验管理的TSH靶向率(Rate1(第一率):52.09%(137/263)对10.53%(28/266);Rate2(累积率):85.55%(225/263)对53.38%(142/266))。此外,该模型显着缩短了达到TSH目标水平的时间(天数)(62.61±58.78vs115.50±71.40)。
    构建的SVR模型可以有效预测RAI治疗后DTC的L-T4剂量,从而缩短DTC患者达到TSH目标水平的时间,提高患者的生活质量。
    UNASSIGNED: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions.
    UNASSIGNED: A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263).
    UNASSIGNED: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40).
    UNASSIGNED: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.
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  • 文章类型: Journal Article
    SPRED3(Sprouty相关的EVH1结构域包含3)突变体在各种癌症中被描述,然而,对其在甲状腺癌(THCA)中的生物学功能一无所知。进行生物信息学分析以确定THCA组织中SPRED3的表达水平及其在THCA患者预后中的重要性。开发Flag-SPRED3质粒和SPRED3敲除载体以在THCA细胞中过表达或耗尽SPRED3表达。使用集落形成测定和CCK8测定检查SPRED3对THCA细胞增殖的功能。SPRED3表达对NF-κB的转录活性的影响也使用荧光素酶报告基因测定来检测。SPRED3高表达与不良临床结局相关,晚期肿瘤特征,和THCA患者甲状腺乳头状癌的传统分子标志物。遗传分析显示,SPRED3高和SPRED3低THCA病例之间关键基因的突变率存在差异。还揭示了SPRED3影响免疫微环境,基质和免疫评分增加,免疫细胞浸润改变。功能上,SPRED3过表达增强THCA细胞活力和集落形成,而其消耗减少细胞生长和增殖。小鼠体内实验证实了SPRED3耗竭对肿瘤生长的抑制作用。机械上,我们发现SPRED3激活了NF-κB信号。第一次,我们发现SPRED3通过NF-κB信号通路促进THCA细胞增殖。这一发现可能有助于深入了解SPRED3在甲状腺癌中的预后潜力,并为SPRED3靶向药物干预提供理论依据。
    SPRED3 (Sprouty-related EVH1 domain containing 3) mutants are depicted in various cancers, however, nothing is known about its biofunction in thyroid cancer (THCA). Bioinformatic analyses were conducted to ascertain the level of SPRED3 expression in THCA tissues and its importance in the prognosis of THCA patients. Flag-SPRED3 plasmid and SPRED3-knockout vector were developed to overexpress or deplete the SPRED3 expression in THCA cells. The function of SPRED3 on THCA cell proliferation was examined using the colony formation assay and CCK8 assay. The effect of SPRED3 expression on the transcriptional activity of NF-κB was also examined using luciferase reporter assays. High SPRED3 expression was associated with unfavorable clinical outcomes, advanced tumor characteristics, and traditional molecular markers of papillary thyroid cancer in THCA patients. Genetic analysis revealed differences in mutation rates in key genes between SPRED3-high and SPRED3-low THCA cases. It is also revealed that SPRED3 influenced the immune microenvironment, with increased stromal and immune scores and altered immune cell infiltration. Functionally, SPRED3 overexpression enhanced THCA cell viability and colony formation, while its depletion reduced cell growth and proliferation. In vivo experiments in mice confirmed the inhibitory effect of SPRED3 depletion on tumor growth. Mechanically, we found that SPRED3 activated the NF-κB signaling. For the first time, we found that SPRED3 promotes THCA cell proliferation via the NF-κB signaling pathway. This finding may provide insight into SPRED3\'s prognostic potential in thyroid cancer and provide the rationale for SPRED3-targeted druggable interventions.
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  • 文章类型: Journal Article
    甲状腺乳头状癌的患病率逐渐增加,年轻化趋势明显。有些病人可能无法接受手术,这是治疗的支柱,由于物理或财务原因。因此,预测非手术甲状腺乳头状癌患者的癌症特异性生存率(CSS)是必要的.
    患者人口统计学和临床信息是从监测中提取的,流行病学,和结束结果数据库。采用SPSS软件进行Cox回归分析和倾向评分匹配分析。使用R软件构建和验证列线图。X-tile软件用于选择患者风险分层的最佳截止点。
    本回顾性研究共纳入1319例患者。经过Cox回归分析,年龄,grade,T级,M阶段,放射治疗,和化疗用于构建列线图。C指数,校正曲线,和接收器工作特性曲线都验证了列线图的高预测精度。决策曲线分析表明,患者可以从该预测模型中获得临床益处。倾向评分匹配后的生存曲线分析显示了放疗对非手术患者CSS的积极影响。
    我们的回顾性研究成功建立了一个列线图,可以准确预测非手术甲状腺乳头状癌患者的CSS,并证明手术患者的放疗仍有助于改善预后。这些发现可以帮助临床医生做出更好的选择。
    UNASSIGNED: The prevalence of papillary thyroid cancer is gradually increasing and the trend of youthfulness is obvious. Some patients may not be able to undergo surgery, which is the mainstay of treatment, due to physical or financial reasons. Therefore, the prediction of cancer-specific survival (CSS) in patients with non-operated papillary thyroid cancer is necessary.
    UNASSIGNED: Patients\' demographic and clinical information was extracted from the Surveillance, Epidemiology, and End Results database. SPSS software was used to perform Cox regression analyses as well as propensity score matching analyses. R software was used to construct and validate the nomogram. X-tile software was used to select the best cutoff point for patient risk stratification.
    UNASSIGNED: A total of 1319 patients were included in this retrospective study. After Cox regression analysis, age, grade, T stage, M stage, radiotherapy, and chemotherapy were used to construct the nomogram. C-index, calibration curves, and receiver operating characteristic curves all verified the high predictive accuracy of the nomogram. The decision curve analysis demonstrated that patients could gain clinical benefit from this predictive model. Survival curve analysis after propensity score matching demonstrated the positive effects of radiotherapy on CSS in non-operated patients.
    UNASSIGNED: Our retrospective study successfully established a nomogram that accurately predicts CSS in patients with non-operated papillary thyroid cancer and demonstrated that radiotherapy for operated patients can still help improve prognosis. These findings can help clinicians make better choices.
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  • 文章类型: Case Reports
    老年人甲状腺结节和恶性肿瘤的患病率日益受到关注。甲状腺结节在这一人群中具有独特的特征,需要谨慎的治疗策略来平衡风险和收益。甲状腺嗜酸细胞癌(OCA)是一种罕见的,具有诊断挑战的侵袭性亚型。
    该病例以一名84岁的患者为特征,该患者表现为颈部肿块和窒息症状。临床评价,影像学检查,进行活检以评估甲状腺病变的性质。分子检测,包括基因分析,进行鉴定与OCA相关的特定突变并指导治疗决策。
    患者被诊断为甲状腺嗜酸细胞癌。分子检测揭示了表明OCA的特定基因突变,确认诊断。这些突变的存在指导了治疗计划,强调分子诊断在治疗甲状腺恶性肿瘤中的重要性,尤其是老年人。
    此病例说明了诊断和治疗老年人甲状腺恶性肿瘤的复杂性。活检和分子检测提供诊断准确性和知情治疗。个性化的方法对于更好的结果至关重要,特别是在侵袭性亚型中,平衡干预的风险和收益。
    UNASSIGNED: The prevalence of thyroid nodules and malignancies in the elderly is a growing concern. Thyroid nodules in this population have unique characteristics, requiring careful treatment strategies that balance risks and benefits. Oncocytic carcinoma of the thyroid (OCA) is a rare, aggressive subtype with diagnostic challenges.
    UNASSIGNED: This case features an 84-year-old patient who presented with a neck mass and symptoms of asphyxia. Clinical evaluation, imaging studies, and biopsy were conducted to assess the nature of the thyroid lesion. Molecular testing, including genetic analysis, was performed to identify specific mutations associated with OCA and guide treatment decisions.
    UNASSIGNED: The patient was diagnosed with oncocytic carcinoma of the thyroid. The molecular testing revealed specific genetic mutations indicative of OCA, confirming the diagnosis. The presence of these mutations guided the treatment plan, emphasizing the importance of molecular diagnostics in managing thyroid malignancies, especially in the elderly.
    UNASSIGNED: This case illustrates the complexities of diagnosing and treating thyroid malignancies in the elderly. Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention.
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