Ewing’s Sarcoma

尤因肉瘤
  • 文章类型: Journal Article
    角化是铜诱导的细胞死亡。铜代谢相关基因(CMRGs)被证明可用于评估肿瘤的预后。在研究中,检测CMRG对尤文氏肉瘤(ES)中TME细胞浸润的影响。
    GEO和ICGC数据库提供了mRNA表达谱和临床特征以供下载。在GSE17674数据集中,通过单变量回归分析鉴定了22个预后相关的铜代谢相关基因(PR-CMRGs)。随后,为了比较这些PR-CMRGs高表达和低表达组的生存率,实施Kaplan-Meier分析。此外,检查了它们之间的相关性。该研究采用功能富集分析来调查可能的潜在途径,而GSVA用于评估ES(表达集)中的富集途径。通过无监督聚类算法,样本被分为两个集群,揭示了存活率和免疫浸润水平的显著差异。
    使用Lasso和逐步回归方法,五个基因(TFRC,SORD,选择SLC11A2、FKBP4和AANAT)作为风险特征。根据Kaplan-Meier生存分析,高危组的生存率明显低于低危组(p=6.013e-09).受试者工作特征(ROC)曲线的曲线下面积(AUC)值分别为1年、3年和5年的0.876、0.883和0.979,分别。在其他数据集中进一步验证了风险模型,即GSE63155、GSE63156和ICGC数据集。为了帮助预测结果,建立了纳入风险水平和临床特征的列线图.此列线图的性能通过校准曲线得到有效验证。此外,该研究评估了不同风险组之间免疫浸润的差异,以及高表达和低表达组。重要的是,确定了几种显示敏感性的药物,为ES提供潜在的治疗选择。
    上述发现强烈表明,CMRGs在预测ES的预后和免疫状态中起着至关重要的作用。
    UNASSIGNED: Cuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing\'s sarcoma (ES).
    UNASSIGNED: The GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.
    UNASSIGNED: Using Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram\'s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.
    UNASSIGNED: The findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.
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  • 文章类型: Journal Article
    尤因肉瘤(EWS)是一种高度侵袭性的恶性骨肿瘤,主要影响青少年和年轻人。尽管在某些情况下放化疗有效,转移性和复发性疾病患者的治愈率仍然很低。因此,迫切需要创新的治疗方法来应对与EWS治疗相关的挑战.表观遗传调控,生理过程中的一个关键因素,在控制细胞增殖中起着重要作用,保持基因完整性,和调节转录。最近的研究强调了异常表观遗传调控在EWS的启动和进展中的重要性。全面了解EWS与异常表观遗传调控之间的复杂相互作用对于推进临床药物开发至关重要。这篇综述旨在全面概述EWS中涉及的两个表观遗传靶标,整合各种治疗方式,为EWS的临床诊断和治疗提供创新的观点。
    Ewing\'s sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.
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  • 文章类型: Case Reports
    背景:小圆细胞肿瘤(SRCT)是一组具有相似光学显微形态的恶性肿瘤。尽管发病率低,SRCT恶性程度高,预后差。此外,不典型的临床症状使术前诊断困难。
    方法:一名67岁男子出现排尿困难,尿流微弱,持续3个月。口服坦索罗辛和非那雄胺治疗2个月后,症状恶化。经尿道前列腺钬激光剥除术,术后病理提示小蓝圆细胞恶性肿瘤。进一步免疫组织化学和荧光原位杂交检查提示尤文样SRCT。因此,进一步进行了达芬奇机器人前列腺切除术,并进行了全基因组测序。几种基因突变包括RAF1,ARID1A,发现了SMARCA4和BCL2L11,但没有FDA批准的药物可以特异性治疗。然后,患者接受了尤因类型的治疗方案治疗,并进行了最新随访(超过24个月)。
    结论:由于其血清PSA水平未升高,前列腺SRCT作为恶性肿瘤的可能性常被忽略,被视为良性前列腺增生(BPH)。如果口服治疗一段时间后排尿困难症状不能明显缓解,则需要考虑前列腺SRCT的可能性。
    BACKGROUND: Small round cell tumor (SRCT) is a group of malignancy with similar optical microscopic morphology. Despite its low incidence, SRCT has a high malignant degree and poor prognosis. Besides, atypical clinical symptoms make it difficult in preoperative diagnosis.
    METHODS: A 67-year-old man was presented to the outpatient service with dysuria and weak urine stream lasting for 3 months. After oral treatment with tamsulosin and finasteride for 2 months, the symptoms worsen. Transurethral prostate holmium laser enucleation was operated and postoperative pathology result revealed small blue round cell malignant tumor. Further immunohistochemistry and fluorescence in situ hybridization examination indicated Ewing-like SRCT. So a Da Vinci Robotic prostatectomy was performed further and whole-genome sequencing was conducted. Several gene mutations including RAF1, ARID1A, SMARCA4, and BCL2L11 were found but no FDA-approved drug could treat specifically. Then the patient received Ewing-type therapeutic regimens treatment and has been followed up to date (over 24 months).
    CONCLUSIONS: Because of its non-elevated serum PSA level, prostate SRCT is often ignored as a possibility of malignant tumor and regarded as benign prostatic hyperplasia (BPH). The possibility of prostate SRCT need to be considered if dysuria symptoms could not alleviate significantly after a period of oral treatment.
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  • 文章类型: Case Reports
    尤因肉瘤,以小圆细胞形态为特征,是一种罕见的恶性肿瘤,纵隔尤因肉瘤更不常见。该病例描述了一名32岁男性的原发性纵隔Ewing肉瘤的独特表现,表现为突然和严重的胸痛。初步评估排除了心脏和肺部急症,通过高级成像显示后纵隔肿块。通过胸腔镜完全切除肿瘤后,患者的临床症状明显改善。结合成像的后续分析,组织学,免疫组织化学和遗传发现导致原发性纵隔尤文氏肉瘤的最终诊断。
    Ewing\'s sarcoma, characterized by small round cell morphology, is a rare malignancy, with mediastinal Ewing\'s sarcoma being even less common. This case describes a distinctive presentation of primary mediastinal Ewing\'s sarcoma in a 32-year-old male presenting with sudden and severe chest pain. Initial evaluation excluded cardiac and pulmonary emergencies, revealing a posterior mediastinal mass through advanced imaging. The patient\'s clinical symptoms significantly improved following the complete resection of the tumor via thoracoscopy. Subsequent analysis incorporating imaging, histological, immunohistochemical and genetic findings led to the conclusive diagnosis of primary mediastinal Ewing\'s sarcoma.
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  • 文章类型: Case Reports
    背景:青少年患者股骨近端恶性骨肿瘤的切除和重建仍然是临床挑战。考虑到青少年的生长发育要求,股骨近端骨缺损的重建没有统一的标准。这里,我们报告一例3D打印钛合金定制假体用于构建股骨近端Ewing肉瘤青少年患者股骨近端骨缺损。病例介绍:一名7岁女性患者因左髋部疼痛被送往当地医院,并被诊断为左股骨近端尤因肉瘤。患者在手术前按照标准方案接受2个疗程的新辅助化疗。考虑到与青少年相关的生长发育问题,我们采用了定制的3D打印股骨近端假体,用于保留患肢的股骨头和部分股骨颈。临床结果,随访12个月后记录,显示受影响肢体的功能恢复良好,功能评分令人满意,没有立即的并发症。结论:3D打印假体是保留股骨头和重建青少年股骨近端骨缺损的可行方法。
    Background: Resection and reconstruction of malignant bone tumors at the proximal femur in adolescent patients has remained a clinical challenge. Considering the growth and development requirements of adolescents, there is no unified standard for the reconstruction of bone defects at the proximal femur. Here, we report a case of 3D-printed titanium alloy customized prosthesis for the construction of proximal femoral bone defects in an adolescent patient with Ewing\'s sarcoma of the proximal femur. Case presentation: A 7-year-old female patient presented to a local hospital with left hip pain, and was diagnosed with Ewing\'s sarcoma on the proximal left femur. The patient received two courses of neoadjuvant chemotherapy before surgery according to the standard protocol. Considering growth and development problems associated with adolescents, we adopted a customized 3D-printed prosthesis of proximal femur for preservation of the femoral head and part of the femoral neck in the affected limb. Clinical outcomes, recorded after 12 months of follow-up, revealed excellent functional recovery and satisfactory functional scores of the affected limb, with no immediate complications. Conclusion: 3D-printed prosthesis is a feasible method for preserving femoral head and reconstruction of bone defects in adolescents\' proximal femur.
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  • 文章类型: Journal Article
    未经证实:尤因肉瘤(ES)是世界范围内最常见的恶性骨肿瘤之一。然而,ES的基因和信号通路的分子机制仍未被充分理解。为了确定参与ES发生和发展的候选基因,本研究采用生物信息学方法筛选与ES相关的关键基因和生物学通路。
    UNASSIGNED:从基因表达综合(GEO)数据库下载GSE45544和GSE17618微阵列数据集。鉴定了差异表达基因(DEGs),并进行了功能富集分析。建立了蛋白质-蛋白质相互作用(PPI)网络,并使用STRING和Cytoscape进行关键模块分析。获得核心基因,并通过验证数据集GSE67886和免疫组织化学(IHC)进行验证。对ES的诊断价值和预后评估,分别,ROC方法和Cox回归。
    未经批准:总共187度,由56个下调基因和131个上调基因组成,通过将肿瘤样品与正常样品进行比较来鉴定。DEGs的丰富功能和途径,包括细胞分裂,有丝分裂核分裂,细胞增殖,细胞周期,卵母细胞减数分裂,和孕激素介导的卵母细胞成熟,进行了分析。PPI网络中有149个节点和1246条边,根据程度水平鉴定出15个hub基因。核心基因(UBE2T)在ES中呈高表达,通过使用GSE67886和IHC验证。ROC分析显示UBE2T在ES中具有突出的诊断价值(训练集中AUC=0.75,验证集中的AUC=0.90)。Kaplan-Meier(生存率分析)和Cox回归分析表明,UBE2T是ES患者不良结果的迹象。
    未经评估:UBE2T是诊断和治疗ES的重要生物标志物,从而为ES提供了一个新的潜在治疗靶点以及评估治疗效果和预后预测的新观点。
    UNASSIGNED: Ewing\'s sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods.
    UNASSIGNED: The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression.
    UNASSIGNED: A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES.
    UNASSIGNED: UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.
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  • 文章类型: Case Reports
    尤因肉瘤是一组罕见的恶性肿瘤的一部分,其病理形态特征是小圆细胞。骨外尤因肉瘤是一种较为少见的原发肿瘤。在这里,我们报告了一例66岁的男性,主诉胸闷。随后的胸部CT扫描显示前纵隔右侧有不规则和不均匀的密度肿块,并侵犯上腔静脉,心包和右肺.在体外循环下进行纵隔病灶切除后,患者的临床症状得到改善。根据组织学和免疫组织化学结果,肿瘤被诊断为骨外尤因肉瘤。
    Ewing\'s sarcoma is a part of a rare group of malignant neoplasms, whose pathological morphological features are small round cells. Extraskeletal Ewing\'s sarcoma is a more uncommon primary tumor. Herein, we report the case of a 66-year-old man who complained of chest tightness. Subsequent chest CT scans revealed an irregular and uneven density mass on the right side of the anterior mediastinum with invasion of the superior vena cava, pericardium and right lung. The patient\'s clinical symptoms were improved after performing excision of the mediastinal lesions under cardiopulmonary bypass. Based on histological and immunohistochemical findings, the tumor was diagnosed as extraskeletal Ewing\'s sarcoma.
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  • 文章类型: Case Reports
    背景:骨外尤文肉瘤(EES)是一种罕见且高度恶性的小圆细胞肿瘤,临床预后较差。累及胃的尤因肉瘤(ES)是一种罕见的表现,很容易与其他小圆形细胞肿瘤混淆。我们在此介绍了一例罕见的涉及胃区的ES病例。
    方法:我们报告了一例19岁女性患者的胃ES,该患者最初表现为5d的上腹部肿块。对比增强的腹部计算机断层扫描显示肝脏和胃之间的软组织密度肿块,直径为8.5cm;肿块与胃窦相连。然后,通过手术将肿块完全切除。根据组织病理学,免疫表型和分子分析,该肿块被鉴定为原发性胃ES。
    结论:EES是一种侵袭性肿瘤,预后较差。因此,早期诊断和及时干预对良好预后至关重要。我们必须提高对这种罕见肿瘤的认识。手术切除仍然是最好的治疗选择。
    BACKGROUND: Extraskeletal Ewing sarcoma (EES) is a rare and highly malignant small round cell tumor associated with a poor clinical outcome. Ewing sarcoma (ES) involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors. We herein present a rare case of ES involving the gastric area.
    METHODS: We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d. Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach; the mass was connected to the gastric antrum. Then, the mass was surgically excised completely. Upon histopathological, immunophenotype and molecular analysis, the mass was identified to be a primary gastric ES.
    CONCLUSIONS: EES is an aggressive tumor with poor prognosis. Therefore, early diagnosis and timely intervention are essential for a good prognosis. It is imperative for us to raise awareness about this rare tumor. Surgical resection is still the best treatment option.
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  • 文章类型: Journal Article
    背景:尤因肉瘤是儿童和青少年第二常见的骨和软组织恶性肿瘤。肿瘤坏死因子-α-诱导蛋白8样1(TIPE1)在几种癌症中作为肿瘤抑制因子发挥作用。肿瘤细胞亚群中Wnt/β-catenin信号的激活有助于尤文氏肉瘤的表型异质性和疾病进展。TIPE1在尤因肉瘤中的确切作用尚待阐明。
    目的:本研究旨在评估TIPE1在尤文氏肉瘤中的表达和功能。
    方法:通过qPCR和western印迹法测定尤文氏肉瘤细胞中TIPE1的表达。此外,用基于慢病毒的TIPE1表达系统转染尤文氏肉瘤细胞系RD-ES以上调TIPE1的表达。细胞计数试剂盒8用于评估TIPE1对细胞增殖的影响。通过Transwell法检测TIPE1对细胞迁移和侵袭的影响。流式细胞术检测细胞凋亡。
    结果:我们的结果表明,与正常骨细胞相比,Ewing肉瘤细胞系中TIPE1的表达较低。TIPE1能显著抑制尤文氏肉瘤细胞的生长和增殖;TIPE1还能诱导细胞凋亡,抑制细胞侵袭。TIPE1抑制尤因肉瘤的生长,运动性,和通过调节Wnt/β-catenin信号传导的存活。
    结论:我们的结果证明了TIPE1在尤因肉瘤中的抗肿瘤功能,并揭示了一个新的治疗靶点。
    BACKGROUND: Ewing\'s sarcoma is the second most common bone and soft tissue malignancy in children and adolescents. Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several cancers. Activation of Wnt/β-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewing\'s sarcoma. The exact role of TIPE1 in Ewing\'s sarcoma remains to be elucidated.
    OBJECTIVE: This study aimed to assess the expression and function of TIPE1 in Ewing\'s sarcoma.
    METHODS: TIPE1 expression in Ewing\'s sarcoma cells was determined by qPCR and western blotting. Furthermore, the Ewing\'s sarcoma cell line RD-ES was transfected with a lentivirus-based TIPE1 expression system to upregulate the expression of TIPE1. The Cell Counting Kit 8 was used to assess the effect of TIPE1 on cell proliferation. The effects of TIPE1 on cell migration and invasion was detected by Transwell assay. Flow cytometry was performed to detect apoptosis.
    RESULTS: Our results suggested lower TIPE1 expression in Ewing\'s sarcoma cell lines compared with normal osseous cells. TIPE1 remarkably inhibited the growth and proliferation of Ewing\'s sarcoma cell; TIPE1 also induced apoptosis and inhibited invasion in vitro. TIPE1 inhibited Ewing\'s sarcoma growth, motility, and survival through regulation of Wnt/β-catenin signaling.
    CONCLUSIONS: Our results demonstrated the anti-tumor function of TIPE1 in Ewing\'s sarcoma and reveal a novel therapeutic target.
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  • 文章类型: Journal Article
    方法:回顾性队列研究。
    目的:本研究旨在开发基于机器学习(ML)的脊柱尤文氏肉瘤(EWS)的生存预测模型。
    方法:我们提取了1975年至2016年诊断的EWS的SEER注册表临床数据。三种特征选择方法提取临床特征。四种ML算法(Cox,随机生存森林(RSF),CoxBoost,DeepCox)接受了训练以预测脊柱EWS的总体生存率(OS)和癌症特异性生存率(CSS)。一致性指数(C指数),使用综合Brier评分(IBS)和平均曲线下面积(AUC)评估不同ML模型的预测性能.从每个评估指标(C-index,最终将IBS和平均AUC)叠加到集成模型中,通过3/5/10年接收器工作特性(ROC)曲线和决策曲线分析(DCA)将其与传统的TNM阶段模型进行比较。
    结果:共发现741例脊柱EWS患者。C指数,在独立测试期间,预测OS的最终集成ML模型的IBS和平均AUC为.693/0.158/0.829,而在预测CSS时.719/0.171/0.819。集成ML模型还实现了.705/0.747/0.851的AUC,用于在独立测试期间预测3-/5-/10年OS,而.734/0.779/0.830用于预测3-/5-/10年CSS,两者都优于传统的TNM阶段。DCA曲线还显示了集成模型相对于传统TNM阶段的优势。
    结论:ML是一种有效且有前景的预测脊柱EWS生存率的技术,集成模型优于传统的TNM阶段模型。
    METHODS: Retrospective Cohort Study.
    OBJECTIVE: This study aimed to develop survival prediction models for spinal Ewing\'s sarcoma (EWS) based on machine learning (ML).
    METHODS: We extracted the SEER registry\'s clinical data of EWS diagnosed between 1975 and 2016. Three feature selection methods extracted clinical features. Four ML algorithms (Cox, random survival forest (RSF), CoxBoost, DeepCox) were trained to predict the overall survival (OS) and cancer-specific survival (CSS) of spinal EWS. The concordance index (C-index), integrated Brier score (IBS) and mean area under the curves (AUC) were used to assess the prediction performance of different ML models. The top initial ML models with best performance from each evaluation index (C-index, IBS and mean AUC) were finally stacked to ensemble models which were compared with the traditional TNM stage model by 3-/5-/10-year Receiver Operating Characteristic (ROC) curves and Decision Curve Analysis (DCA).
    RESULTS: A total of 741 patients with spinal EWS were identified. C-index, IBS and mean AUC for the final ensemble ML model in predicting OS were .693/0.158/0.829 during independent testing, while .719/0.171/0.819 in predicting CSS. The ensemble ML model also achieved an AUC of .705/0.747/0.851 for predicting 3-/5-/10-year OS during independent testing, while .734/0.779/0.830 for predicting 3-/5-/10-year CSS, both of which outperformed the traditional TNM stage. DCA curves also showed the advantages of the ensemble models over the traditional TNM stage.
    CONCLUSIONS: ML was an effective and promising technique in predicting survival of spinal EWS, and the ensemble models were superior to the traditional TNM stage model.
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