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在手术切除前,恶性胶质瘤患者的神经认知功能因异柠檬酸脱氢酶1(IDH1)基因突变状态而异。

Neurocognitive function varies by IDH1 genetic mutation status in patients with malignant glioma prior to surgical resection.

作者信息

Wefel Jeffrey S, Noll Kyle R, Rao Ganesh, Cahill Daniel P

机构信息

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.S.W., K.R.N); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (G.R.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (D.P.C.)

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (J.S.W., K.R.N); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (G.R.); Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (D.P.C.).

出版信息

Neuro Oncol. 2016 Dec;18(12):1656-1663. doi: 10.1093/neuonc/now165. Epub 2016 Aug 30.


DOI:10.1093/neuonc/now165
PMID:27576872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5744240/
Abstract

BACKGROUND: Patients with malignant gliomas present with variation in neurocognitive function (NCF) not attributable to lesion size or location alone. A potential contributor is the rate at which tumors grow, or "lesion momentum." Isocitrate dehydrogenase 1 wild type (IDH1-WT) are more proliferative and aggressive than IDH1-mutant (IDH1-M) tumors. We hypothesized that patients with IDH1-WT would exhibit worse NCF than patients with IDH1-M tumors. METHODS: Comprehensive NCF testing was completed in 119 patients with malignant glioma prior to surgical resection. IDH1 status was determined with immunohistochemistry and sequencing. Rates of impairment and mean test performances were compared by IDH1. RESULTS: NCF impairment was significantly more frequent in patients with IDH1-WT tumors in memory, processing speed, visuoconstruction, language, executive functioning, and manual dexterity. Mean performances of patients with IDH1-WT were also significantly lower than those with IDH1-M tumors on measures of learning and memory, processing speed, language, executive functioning, and dexterity. Lesion volume was not statistically different between IDH1-WT and IDH1-M tumors. Tumor and lesion volume on T1-weighted and fluid attenuated inversion recovery MRI were significantly associated with most NCF tests in patients with IDH1-WT, but only significantly associated with a single measure in patients with IDH1-M tumors. CONCLUSION: Patients with IDH1-WT show reduced NCF compared with those with IDH1-M malignant gliomas. Lesion volume is inversely associated with NCF for patients with IDH1-WT, but not IDH1-M tumors. These findings are consistent with the hypothesis that patients with IDH1-WT tumors present with more severe NCF impairment due to greater lesion momentum, which may impede compensatory neuroplasticity and cerebral reorganization.

摘要

背景:恶性胶质瘤患者的神经认知功能(NCF)存在差异,这种差异并非仅由病变大小或位置所致。一个潜在因素是肿瘤生长速度,即“病变进展”。异柠檬酸脱氢酶1野生型(IDH1-WT)肿瘤比IDH1突变型(IDH1-M)肿瘤更具增殖性和侵袭性。我们假设IDH1-WT患者的NCF比IDH1-M肿瘤患者更差。 方法:对119例恶性胶质瘤患者在手术切除前进行了全面的NCF测试。通过免疫组织化学和测序确定IDH1状态。按IDH1比较损伤率和平均测试表现。 结果:IDH1-WT肿瘤患者在记忆、处理速度、视觉构建、语言、执行功能和手动灵活性方面的NCF损伤明显更频繁。在学习和记忆、处理速度、语言、执行功能和灵活性测量方面,IDH1-WT患者的平均表现也明显低于IDH1-M肿瘤患者。IDH1-WT和IDH1-M肿瘤之间的病变体积无统计学差异。T1加权和液体衰减反转恢复MRI上的肿瘤和病变体积与IDH1-WT患者的大多数NCF测试显著相关,但仅与IDH1-M肿瘤患者的一项测量显著相关。 结论:与IDH1-M恶性胶质瘤患者相比,IDH1-WT患者的NCF降低。病变体积与IDH1-WT患者的NCF呈负相关,但与IDH1-M肿瘤患者无关。这些发现与以下假设一致,即IDH1-WT肿瘤患者由于更大的病变进展而表现出更严重的NCF损伤,这可能会阻碍代偿性神经可塑性和大脑重组。

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[1]
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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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[6]
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[7]
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Neurooncol Adv. 2025-1-8

[8]
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Neurooncol Pract. 2024-10-19

[9]
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[10]
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本文引用的文献

[1]
Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

Cell. 2016-1-28

[2]
Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.

N Engl J Med. 2015-6-25

[3]
Relationships between tumor grade and neurocognitive functioning in patients with glioma of the left temporal lobe prior to surgical resection.

Neuro Oncol. 2015-4

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Diffuse low-grade gliomas and neuroplasticity.

Diagn Interv Imaging. 2014-10

[5]
Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status.

Neuro Oncol. 2014-6

[6]
Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing.

J Neurooncol. 2014-6

[7]
IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection.

Neuro Oncol. 2013-12-4

[8]
IDH1 mutation is associated with improved overall survival in patients with glioblastoma: a meta-analysis.

Tumour Biol. 2013-12

[9]
IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma.

Neuro Oncol. 2013-7-21

[10]
Subgrouping of gliomas on the basis of genetic profiles.

Brain Tumor Pathol. 2013-4-20

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