low-grade glioma

低度胶质瘤
  • 文章类型: Case Reports
    磁共振成像(MRI)是神经外科不可缺少的工具,尽管它有时会面临诸如“肿瘤模仿”之类的挑战。“虽然术中MRI(iMRI)因其在神经胶质瘤手术期间实现最大安全切除的有用性而被广泛认可,iMRI上仍存在肿瘤拟态的情况。此外,关于通过iMRI观察到的肿瘤模拟物的报告,特别是在低级别胶质瘤中,保持稀缺。在这篇文章中,我们介绍了一个少突胶质细胞瘤的病例,iMRI上新出现的T2高信号强度区域需要区分肿瘤扩张。一名23岁的男子出现了新诊断的脑肿瘤,并接受了手术切除。肿瘤切除后的iMRI显示,切除腔周围有一个新出现的T2高强度区,没有扩散限制。在术前MRI中未观察到。怀疑肿瘤残留,我们进行了额外的切除.第二天的MRI证实iMRI上确定的T2高信号区域已被完全切除,但也显示了更宽区域的T2高信号区域扩大。组织病理学在额外切除的区域没有发现肿瘤细胞,表明iMRI发现是肿瘤模拟。六个月后,切除腔周围的T2高信号区域在没有任何额外治疗的情况下在MRI上消失.这种情况突出了在iMRI上看到的神经胶质瘤手术期间区分T2高强度拟态和肿瘤增大的挑战。尽管iMRI具有重要价值,我们的报告强调了在神经外科实践中需要仔细解释,特别是非对比增强肿瘤。
    Magnetic resonance imaging (MRI) is an indispensable tool in neurosurgery, though it sometimes faces challenges such as \"tumor mimicry.\" While intraoperative MRI (iMRI) is widely recognized for its usefulness in achieving maximal safe resection during glioma surgery, instances of tumor mimicry still occur on iMRI. Moreover, reports on tumor mimics observed through iMRI, particularly in low-grade gliomas, remain scarce. In this article, we present a case of oligodendroglioma, where a newly emerged T2 high-signal intensity region on iMRI necessitated differentiation from tumor expansion. A 23-year-old man presented with a newly diagnosed brain tumor and underwent surgical removal. An iMRI taken after tumor removal revealed a newly emerged T2 hyperintense area without diffusion restriction around the resection cavity, which was not observed in the preoperative MRI. Suspecting residual tumor, we performed additional resection. An MRI on the following day confirmed that the T2 hyperintense area identified on the iMRI had been completely resected but also revealed an enlarged T2 high-signal area over a wider region. Histopathology found no tumor cells in the additionally resected area, indicating that the iMRI finding was a tumor mimic. Six months later, the T2 high-signal area around the resection cavity had disappeared on MRI without any additional treatment. This case highlights the challenge of distinguishing between T2 hyperintense mimicry and tumor enlargement during glioma surgery seen on iMRI. Despite the significant value of iMRI, our report underscores the need for careful interpretation in neurosurgical practice, particularly with non-contrast-enhancing tumors.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    癫痫发作通常会给低度胶质瘤(LGG)患者带来负担,并对生活质量产生负面影响。神经认知,和一般患者健康。抗癫痫药物(ASM)用于控制癫痫发作,但可能导致不希望的副作用。我们的目的是报告我们在LGG患者最大病例系列之一(根据WHO2021分类重新分类)中的癫痫经历。此外,我们评估了术前使用ASM的LGG患者和未使用ASM的LGG患者的术后癫痫发作频率差异。
    数据从2006年至2022年的Salford皇家医院电子记录和神经肿瘤学数据库中回顾性收集。进行了描述性统计以进行人口统计学分析,而多变量分析用于确定术后无癫痫发作结局。
    总共,206例患者共进行257例手术。术后,114名患者癫痫发作,大约45.2%的患者在术后3-12个月出现癫痫发作,术前使用ASM的患者的几率更高。没有证据表明清醒开颅手术的患者术后癫痫发作率高于全身麻醉。切除程度(EOR)与癫痫发作失败呈负相关,与所有其他手术切除相比,总体全切除显示癫痫发作在统计学上显着减少。
    根据我们的经验,术前处方ASM时,没有证据表明术后癫痫发作结局降低.EOR是术后癫痫发作失败的独立预测指标,所有其他变量均无显著性.总的来说,一项更大的研究可以更详细地研究ASM在LGG中的作用.
    UNASSIGNED: Epileptic seizures commonly burden low-grade glioma (LGG) patients and negatively impact quality of life, neurocognition, and general patient health. Anti-seizure medications (ASMs) are used to manage seizures but can result in undesired side effects. Our aim was to report our experience in epilepsy in one of the largest case series of LGG patients (reclassified in accordance with the WHO 2021 classification). Furthermore, we evaluate our postoperative seizure frequency difference between LGG patients who use preoperative ASMs and ones with no ASMs.
    UNASSIGNED: Data were retrospectively collected from Salford Royal Hospital electronic records and Neuro-Oncology database from 2006 to 2022. Descriptive statistics were performed for demographic analysis, while multivariable analysis was used to determine postoperative seizure-free outcomes.
    UNASSIGNED: In total, 257 operations were performed on 206 patients. Postoperatively, 114 patients suffered from seizures, and approximately 45.2% of patients developed seizures at 3-12 months postsurgery, with the odds higher in patients on preoperative ASMs. There was no evidence to suggest a higher postoperative seizure rate in patients undergoing awake craniotomy versus general anesthetic. The extent of resection (EOR) was inversely related to seizure failure, with gross-total resection showing a statistically significant reduction in seizures in comparison to all other surgical resections.
    UNASSIGNED: In our experience, there is no evidence to suggest a reduced postoperative seizure outcome when prescribing preoperative ASMs. EOR is an independent prognosticator for postoperative seizure failure with all other variables demonstrating nonsignificance. Overall, a larger study can investigate the role of ASMs in LGG in greater detail.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    放射治疗(RT)在低度胶质瘤(LGG)的治疗中起着不可或缺的作用。RT的晚期毒性可引起进行性神经认知功能障碍。辐射引起的海马(HCP)损伤在记忆力下降中起着重要作用。光子规划软件的进步导致了多标准优化(MCO)和HyperArc技术的发展,这些技术可以改善HCP的节省,同时保持规划目标体积(PTV)目标覆盖范围。
    比较了三种海马保留(HS)的计划方法,体积调制电弧治疗(VMAT)无HS(VMAT_noHS),带HS的VMAT(VMAT_HS),MCO带HS(MCO_HS),和带HS的HyperArc(HyperArc_HS)。
    确定了25名患者。16例患者保留对侧HCP,9例肿瘤位于上方的患者保留双侧HCP。在对侧病例中,所有3种HS计划技术均显示出备用HCP的剂量显着减少,但在双侧病例中只有VMAT_HS和MCO_HS达到了这一点(P<.008)。在所有测量指标中,仅MCO_HS在降低对侧HCP和双侧HCP的剂量方面优于VMAT_HS(P<.008)。所有计划均实现了PTV和OAR(危险器官)剂量限制。
    这项回顾性剂量学研究证明了HS治疗低度胶质瘤的可行性。所有3种HS计划技术均实现了对保留的对侧海马的显着剂量减少,但在双边病例中,只有MCO_HS和VMAT_HS做到了这一点。MCO在保留双侧和对侧海马方面优于其他计划技术。
    UNASSIGNED: Radiotherapy (RT) plays an integral role in the management of low-grade gliomas (LGG). Late toxicity from RT can cause progressive neurocognitive dysfunction. Radiation-induced damage to the hippocampus (HCP) plays a considerable role in memory decline. Advancements in photon planning software have resulted in the development of multi-criteria optimization (MCO) and HyperArc technologies which may improve HCP sparing while maintaining planning target volume (PTV) target coverage.
    UNASSIGNED: Three planning methods for hippocampal sparing (HS) were compared, volumetric modulated arc therapy (VMAT) without HS (VMAT_noHS), VMAT with HS (VMAT_HS), MCO with HS (MCO_HS), and HyperArc with HS (HyperArc_HS).
    UNASSIGNED: Twenty-five patients were identified. The contralateral HCP was spared in 16 patients and bilateral HCP in 9 patients with superiorly located tumors. All 3 HS planning techniques showed significant reductions in dose to the spared HCP in contralateral cases but only VMAT_HS and MCO_HS achieved this in bilateral cases (P < .008). Only MCO_HS was superior to VMAT_HS in lowering the dose to both contralateral HCP and bilateral HCP in all measured metrics (P < .008). PTV and OAR (organ at risk) dose constraints were achieved for all plans.
    UNASSIGNED: This retrospective dosimetric study demonstrated the feasibility of HS for low-grade glioma. All 3 HS planning techniques achieved significant dose reductions to the spared contralateral hippocampus, but only MCO_HS and VMAT_HS achieved this in bilateral cases. MCO was superior to other planning techniques for sparing both bilateral and contralateral hippocampi.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    WEE1是DNA损伤反应途径中的关键激酶,已被证明可有效治疗浆液性子宫癌。然而,它在神经胶质瘤中的作用,特别是低级别胶质瘤(LGG),尚不清楚。DNA甲基化对神经胶质瘤中WEE1表达的影响及其与免疫景观的相关性也需要进一步研究。
    这项研究使用了来自癌症基因组图谱(TCGA)的数据,中国胶质瘤基因组图谱(CGGA),和基因表达综合(GEO),并利用各种生物信息学工具来分析基因表达,生存,基因相关性,免疫评分,免疫浸润,基因组改变,肿瘤突变负荷,微卫星不稳定,胶质瘤患者的临床特征,WEE1DNA甲基化,预后分析,胶质瘤组织样本中的单细胞基因表达分布,和基于WEE1表达的免疫治疗反应预测。
    WEE1在LGG和胶质母细胞瘤(GBM)中上调,但与其他癌症相比,它对LGG的预后影响更大。高WEE1表达与LGG预后较差相关,特别是当与野生型IDH组合时。WEE1抑制剂MK-1775有效抑制LGG细胞系的增殖和迁移,对WEE1抑制更敏感。DNA甲基化负调控WEE1,且WEE1的高DNA高甲基化与LGG比GBM更好的预后相关。结合WEE1抑制和DNA甲基转移酶抑制显示出协同作用。此外,WEE1下调对免疫治疗反应具有良好的预测价值.共表达网络分析确定了参与WEE1介导的免疫景观调节的关键基因,分化,和LGG转移。
    我们的研究表明,WEE1是靶向治疗和预后评估的有希望的指标。值得注意的是,在LGG和GBM之间观察到WEE1的作用存在显着差异。对WEE1抑制的进一步研究,与DNA甲基转移酶抑制或免疫疗法联合使用,在LGG的背景下是有保证的。
    UNASSIGNED: WEE1 is a critical kinase in the DNA damage response pathway and has been shown to be effective in treating serous uterine cancer. However, its role in gliomas, specifically low-grade glioma (LGG), remains unclear. The impact of DNA methylation on WEE1 expression and its correlation with the immune landscape in gliomas also need further investigation.
    UNASSIGNED: This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) and utilized various bioinformatics tools to analyze gene expression, survival, gene correlation, immune score, immune infiltration, genomic alterations, tumor mutation burden, microsatellite instability, clinical characteristics of glioma patients, WEE1 DNA methylation, prognostic analysis, single-cell gene expression distribution in glioma tissue samples, and immunotherapy response prediction based on WEE1 expression.
    UNASSIGNED: WEE1 was upregulated in LGG and glioblastoma (GBM), but it had a more significant prognostic impact in LGG compared to other cancers. High WEE1 expression was associated with poorer prognosis in LGG, particularly when combined with wild-type IDH. The WEE1 inhibitor MK-1775 effectively inhibited the proliferation and migration of LGG cell lines, which were more sensitive to WEE1 inhibition. DNA methylation negatively regulated WEE1, and high DNA hypermethylation of WEE1 was associated with better prognosis in LGG than in GBM. Combining WEE1 inhibition and DNA methyltransferase inhibition showed a synergistic effect. Additionally, downregulation of WEE1 had favorable predictive value in immunotherapy response. Co-expression network analysis identified key genes involved in WEE1-mediated regulation of immune landscape, differentiation, and metastasis in LGG.
    UNASSIGNED: Our study shows that WEE1 is a promising indicator for targeted therapy and prognosis evaluation. Notably, significant differences were observed in the role of WEE1 between LGG and GBM. Further investigation into WEE1 inhibition, either in combination with DNA methyltransferase inhibition or immunotherapy, is warranted in the context of LGG.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    胶质瘤,一种主要类型的脑肿瘤,可能是致命的。这需要早期诊断和有效的治疗策略。目前的诊断是基于活检,提示需要非侵入性神经成像替代方案。扩散张量成像(DTI)是研究肿瘤对白质(WM)组织的病理生理影响的一种有前途的方法。在脑胶质瘤患者中的单壳DTI研讨还没有解释由于肿瘤而产生的游离水(FW)沾染。本研究旨在(a)评估考虑FW污染的两室DTI模型的功效,以及(b)鉴定基于DTI的生物标志物以对低级别神经胶质瘤(LGG)和高级别神经胶质瘤(HGG)患者进行分类。使用常规临床成像方案获得来自86名患者(LGGn=39,HGGn=47)的DTI数据。评估了肿瘤区域和正常出现的白质(NAWM)的DTI指标。采用先进的基于堆叠的集成学习,使用单室和两室DTI模型措施对LGG和HGG患者进行分类。两室模型的DTI指标在灵敏度方面优于标准单室DTI模型,特异性,和受试者工作特征曲线下面积(AUC-ROC)评分对LGG和HGG患者进行分类。四个功能(16个功能中的),即水肿和核心区域的各向异性分数(FA)以及NAWM区域的FA和平均扩散率,表现出卓越的性能(灵敏度=92%,特异性=90%,和AUC-ROC=90%)在LGG和HGG分类中。这表明,在LGG和HGG患者中,肿瘤和NAWM区域可能会受到不同程度的影响。我们的结果证明了使用两室DTI模型通过提高诊断准确性来解决FW污染的重要性。这种改善最终可能有助于规划神经胶质瘤患者的治疗策略。
    Glioma, a predominant type of brain tumor, can be fatal. This necessitates an early diagnosis and effective treatment strategies. Current diagnosis is based on biopsy, prompting the need for non invasive neuroimaging alternatives. Diffusion tensor imaging (DTI) is a promising method for studying the pathophysiological impact of tumors on white matter (WM) tissue. Single-shell DTI studies in brain glioma patients have not accounted for free water (FW) contamination due to tumors. This study aimed to (a) assess the efficacy of a two-compartment DTI model that accounts for FW contamination and (b) identify DTI-based biomarkers to classify low-grade glioma (LGG) and high-grade glioma (HGG) patients. DTI data from 86 patients (LGG n = 39, HGG n = 47) were obtained using a routine clinical imaging protocol. DTI metrics of tumorous regions and normal-appearing white matter (NAWM) were evaluated. Advanced stacked-based ensemble learning was employed to classify LGG and HGG patients using both single- and two-compartment DTI model measures. The DTI metrics of the two-compartment model outperformed those of the standard single-compartment DTI model in terms of sensitivity, specificity, and area under the curve of receiver operating characteristic (AUC-ROC) score in classifying LGG and HGG patients. Four features (out of 16 features), namely fractional anisotropy (FA) of the edema and core region and FA and mean diffusivity of the NAWM region, showed superior performance (sensitivity = 92%, specificity = 90%, and AUC-ROC = 90%) in classifying LGG and HGG. This demonstrates that both tumorous and NAWM regions may be differentially affected in LGG and HGG patients. Our results demonstrate the significance of using a two-compartment DTI model that accounts for FW contamination by improving diagnostic accuracy. This improvement may eventually aid in planning treatment strategies for glioma patients.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    胶质瘤切除术旨在最大程度地切除肿瘤,同时保留神经功能。神经导航系统(NS),术中成像,通过精确的肿瘤定位和详细的解剖导航彻底改变了这一过程。
    为了评估神经导航和术中影像学在神经胶质瘤切除术中的疗效和广度,确定运营挑战,并为医学生和非神经外科医生提供有关其实际应用的教育见解。
    本系统综述分析了2012年至2023年在神经导航下接受手术切除的神经胶质瘤患者的研究,来自MEDLINE(PubMed),Embase,和WebofScience。采用了特定于数据库的搜索策略,独立审稿人使用Rayyan筛选资格,并使用JoannaBriggsInstitute(JBI)工具提取数据。
    神经导航系统与术中成像模式如iMRI的整合,IUS,和5-ALA可显着提高总切除率(GTR)和切除程度(EOR)。虽然先进的技术提高了手术效果,它并没有普遍减少手术时间,对长期生存的影响各不相同。与单独使用NS相比,NS+iMRI和NS+5-ALA+iMRI等组合可获得更高的GTR率。这表明先进的影像学辅助手段提高了肿瘤切除的准确性和成功率。结果强调了成功手术结果的多面性。
    术中成像与神经导航相结合可改善神经胶质瘤切除。持续的研究对于完善技术至关重要,提高准确性,降低成本,改进培训,考虑影响患者生存的各种因素。
    UNASSIGNED: Glioma resection aims for maximal tumor removal while preserving neurological function. Neuronavigation systems (NS), with intraoperative imaging, have revolutionized this process through precise tumor localization and detailed anatomical navigation.
    UNASSIGNED: To assess the efficacy and breadth of neuronavigation and intraoperative imaging in glioma resections, identify operational challenges, and provide educational insights to medical students and non-neurosurgeons regarding their practical applications.
    UNASSIGNED: This systematic review analyzed studies from 2012 to 2023 on glioma patients undergoing surgical resection with neuronavigation, sourced from MEDLINE (PubMed), Embase, and Web of Science. A database-specific search strategy was employed, with independent reviewers screening for eligibility using Rayyan and extracting data using the Joanna Briggs Institute (JBI) tool.
    UNASSIGNED: The integration of neuronavigation systems with intraoperative imaging modalities such as iMRI, iUS, and 5-ALA significantly enhances gross total resection (GTR) rates and extent of resection (EOR). While advanced technology improves surgical outcomes, it does not universally reduce operative times, and its impact on long-term survival varies. Combinations like NS + iMRI and NS + 5-ALA + iMRI achieve higher GTR rates compared to NS alone, indicating that advanced imaging adjuncts enhance tumor resection accuracy and success. The results underscore the multifaceted nature of successful surgical outcomes.
    UNASSIGNED: Integrating intraoperative imaging with neuronavigation improves glioma resection. Ongoing research is vital to refine technology, enhance accuracy, reduce costs, and improve training, considering various factors impacting patient survival.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    在低级别神经胶质瘤中,免疫治疗方案并不常见,尽管此类疗法可能对无法手术和侵袭性病例有益。对低度神经胶质瘤中的免疫和基质细胞的了解与此类方法高度相关,但仍需改进。收集了来自400个低级别神经胶质瘤和193个高级别神经胶质瘤的已发布基因表达数据,以使用明确为脑肿瘤设计的去卷积方法来量化10个微环境细胞群。首先,我们调查了低级别和高级别胶质瘤微环境的一般差异.低级和高级肿瘤聚集在一起,分别,并显示出这些群体之间的总体相似性和明显差异,主要差异是高级别胶质瘤中成纤维细胞和T细胞的浸润较高。在分析的实体中,神经节胶质瘤和多形性黄色星形细胞瘤表现出最高的整体免疫细胞浸润。对低级别神经胶质瘤的进一步分析显示了免疫细胞浸润的三个不同的微环境特征,可以分为T细胞/树突状/自然杀伤细胞-,嗜中性/B谱系/自然杀伤细胞-,和单核细胞/血管/基质细胞为主的免疫簇。这些簇与肿瘤位置相关,年龄,和组织学诊断,但与性别或无进展生存期无关。生存分析显示,可以从基因表达预测预后,临床资料,以及两者与支持向量机的组合,并揭示了血管标志物的负面预后相关性。总的来说,我们的工作表明,低度和高度胶质瘤可以通过其免疫细胞浸润来表征和分化。低级别神经胶质瘤聚集到三个不同的免疫肿瘤微环境中,这可能对即将到来的免疫治疗研究有进一步的兴趣。
    Immunologic treatment options are uncommon in low-grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge of the immune and stromal cells in low-grade gliomas is highly relevant for such approaches but still needs to be improved. Published gene-expression data from 400 low-grade gliomas and 193 high-grade gliomas were gathered to quantify 10 microenvironment cell populations with a deconvolution method designed explicitly for brain tumors. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T cells in high-grade gliomas. Among the analyzed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-cell-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis but not with sex or progression-free survival. A survival analysis showed that the prognosis can be predicted from gene expression, clinical data, and a combination of both with a support vector machine and revealed the negative prognostic relevance of vascular markers. Overall, our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low-grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    弥漫性低度胶质瘤(LGG)生长的放射学随访具有挑战性。由于病理学的复杂性,近似视觉评估仍然优于客观量化。渗透的性格,弥漫性边界和手术腔的存在需要基于LGG的线性测量规则,以有效和精确地评估LGG随时间的演变。
    我们比较了优化的一维,2D,和手动体积分割的3D线性测量作为参考,以评估36例LGG患者的LGG肿瘤生长(340次磁共振成像扫描),使用临床重要的平均肿瘤直径(MTD)和速度直径扩展(VDE)。使用基于高级别神经胶质瘤的RECIST建立LGG特异性进展阈值,麦克唐纳,和RANO标准,将每种线性方法的识别进展/非进展的灵敏度与手动分割建立的地面实况进行比较。
    3D线性体积近似与手动分割体积密切相关。它还显示了进展检测的最高灵敏度。MTD显示了相当的结果,而VDE强调,在具有多个残基的小肿瘤的情况下,谨慎是必要的。新型LGG特异性进展阈值,或者估计肿瘤体积的关键变化,对于3D方法(从40%增加到52%)和2D方法(从25%减少到33%),对于1D方法(从20%减少到16%)。使用3D方法允许~5分钟的时间增益。
    虽然手动体积评估仍然是计算增长率的黄金标准,3D线性方法是常规使用的LGGs放射学评估的最佳时效性标准化替代方法。
    UNASSIGNED: Radiological follow-up of diffuse low-grade gliomas (LGGs) growth is challenging. Approximative visual assessment still predominates over objective quantification due to the complexity of the pathology. The infiltrating character, diffuse borders and presence of surgical cavities demand LGG-based linear measurement rules to efficiently and precisely assess LGG evolution over time.
    UNASSIGNED: We compared optimized 1D, 2D, and 3D linear measurements with manual volume segmentation as a reference to assess LGG tumor growth in 36 patients with LGG (340 magnetic resonance imaging scans), using the clinically important mean tumor diameter (MTD) and the velocity diameter expansion (VDE). LGG-specific progression thresholds were established using the high-grade gliomas-based RECIST, Macdonald, and RANO criteria, comparing the sensitivity to identify progression/non-progression for each linear method compared to the ground truth established by the manual segmentation.
    UNASSIGNED: 3D linear volume approximation correlated strongly with manually segmented volume. It also showed the highest sensitivity for progression detection. The MTD showed a comparable result, whereas the VDE highlighted that caution is warranted in the case of small tumors with multiple residues. Novel LGG-specific progression thresholds, or the critical change in estimated tumor volume, were increased for the 3D (from 40% to 52%) and 2D methods (from 25% to 33%) and decreased for the 1D method (from 20% to 16%). Using the 3D method allowed a ~5-minute time gain.
    UNASSIGNED: While manual volumetric assessment remains the gold standard for calculating growth rate, the 3D linear method is the best time-efficient standardized alternative for radiological evaluation of LGGs in routine use.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    低级别胶质瘤(LGG)是II-III级胶质瘤,具有独特的临床和分子特征,其预后相关研究尚不清楚。本研究的目的是探讨线粒体相关基因SLBP的参与,COMMD7,LSM4,TOMM34,RPP40,FKBP1A,ARPC1A,和TBCA用于LGG的预后。我们通过分析生物信息学数据集并将其与RT-PCR实验相结合来检测某些基因表达的差异。随后,构建了一个列线图,并验证了风险因素的临床相关性,如年龄,WHO等级,IDH突变状态,Ch.1p19q共同删除状态,和ARPC1A的高表达和低表达来预测1-,3-,ARPC1A的5年总生存率和预后相关性。对与ARPC1A表达相关的相关数据集进行基因集富集分析,以通过KEGG和GO分析阐明LGG中涉及的癌症促进途径。转染测定,CCK-8测定,和流式细胞术用于确定增殖率,HS683和SW1783细胞系的凋亡率。Western印迹用于检查ARPC1A通过MAPK信号传导的癌症促进活性的参与。在这项研究中,通过生物信息学分析结合实验方法分析发现,ARPC1A在LGG中的预后价值可能是一个显著的独立危险因素。ARPC1A促进更高的LGG增殖率,可以控制MAP激酶信号传导,并且可能是LGG的重要生物标志物。未来的研究有必要探讨其临床意义。
    Low-grade glioma (LGG) is a grade II-III glioma accompanied by distinct clinical and molecular characteristics and the studies related to its prognosis are still unclear. The objective of this study is to explore the involvement of mitochondrial-related genes SLBP, COMMD7, LSM4, TOMM34, RPP40, FKBP1A, ARPC1A, and TBCA for the prognosis of LGG. We detected differences in the expression of some of the genes by analyzing the bioinformatics dataset and combining it with RT-PCR experiments. Subsequently, a nomogram was constructed and validated for the clinical relevance of risk factors such as age, WHO grade, IDH mutation status, Ch.1p19q co-deletion status, and high and low expression of ARPC1A to predict the 1-, 3-, 5-year overall survival and prognostic relevance of ARPC1A. Gene set enrichment analysis was performed for the relevant datasets pertinent to the expression of ARPC1A to elucidate the cancer-promoting pathways involved in the LGG through KEGG and GO analysis. Transfection assays, CCK-8 assays, and flow cytometry were used to determine the proliferation rate, and apoptosis rate of the HS683 and SW1783 cell lines respectively. Western blotting was used to examine the involvement of the cancer-promoting activity of ARPC1A through MAPK signaling. In this study, the prognostic value of ARPC1A in LGG was found by bioinformatics analysis combined with experimental approach analysis and may be a significant independent risk factor. ARPC1A fosters a higher LGG proliferation rate that may control the MAP kinase signaling and could be a prominent biomarker for LGG. Future studies are warranted to explore its clinical implications.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    肿瘤可能含有数十亿个细胞,包括不同的恶性克隆和非恶性细胞类型。澄清进化史,患病率,确定这些细胞的分子特征对于改善临床结果至关重要,因为肿瘤内异质性为获得对靶向治疗的抵抗提供了燃料。在这里,我们提出了一种基于统计学的策略,通过对连续肿瘤切片(MOMA)的多体和多尺度分析来解构肿瘤内异质性。通过将IDH突变型星形细胞瘤的深度采样与单核苷酸变体的整合分析相结合,拷贝数变体,和基因表达,我们重建和验证系统发育,空间分布,和不同恶性克隆的转录谱。通过对单核RNA-seq分析的核进行基因分型,我们进一步表明,从单细胞转录组识别癌细胞的常用算法可能不准确。我们还证明,将大量样品中的基因表达与肿瘤纯度相关联可以揭示恶性细胞的最佳标志物,并使用这种方法来鉴定星形细胞瘤躯干克隆一致表达的一组核心基因。包括AKR1C3,其表达与几种癌症的不良预后相关。总之,MOMA提供了一种强大而灵活的策略,可以精确地解构肿瘤内异质性,并阐明实体瘤中不同细胞群的核心分子特性。
    Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that are consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号