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通过检测非整倍体细胞鉴定神经胶质瘤外周血中的循环肿瘤细胞

[Identification of circulating tumor cells in peripheral blood for gliomas by detection of aneuploid cells].

作者信息

Li M X, Ren X H, Jiang H H, Yang K Y, Lin S, Cui Y

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Beijing Institute of Neurosurgery, Beijing 100070, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2019 Apr 16;99(15):1184-1188. doi: 10.3760/cma.j.issn.0376-2491.2019.15.013.

Abstract

To investigate the feasibility of detecting circulating tumor cells based on capture of heteroploid chromosome cells in peripheral blood of glioma patients. A total of 88 patients who were considered to suffer from gliomas and 10 healthy volunteers were enrolled in this study during January 2016 to December 2016 at Beijing Tiantan Hospital, from whom 6 ml preoperative blood was collected. Subtraction enrichment (SE)-immunostaining FISH (iFISH) was applied to capture the heteroploid chromosome 8 cells in those samples. Meanwhile, centromere probe 8(CEP-8)-FISH was used to identify aneuploid cells in 10 tumors and 10 brain tissues. Numerous heteroploid chromosome 8 cells were observed in tumors whereas negative result was present in brain tissues (0.01). CTC was successfully detected in 90.9% glioma patients, in contrast, only one healthy volunteer was shown with a heteroploid chromosome 8 cell (0.01). Glial fibrillary acidic protein was not exhibited in the overwhelming majority of CTC (96.1%). High grade glioma (HGG) without IDH mutation possessed much more CTC than low grade (12.0 vs 2.2), 0.01. Furthermore, multiploidy (≥5 copies) CTC accounted for a much significant percentage in HGG, either in tumors originating from oligodendrocyte or astrocyte (75.9% vs 56.0%), 0.01; 62.7% vs 51.7%, 0.016, respectively). CTC could be identified and enumerated in glioma by detecting aneuploidy cells in blood. The number and multiploidy proportion of CTC may be correlative with tumor grade and molecular characteristics.

摘要

探讨基于捕获胶质瘤患者外周血中异倍体染色体细胞来检测循环肿瘤细胞的可行性。2016年1月至2016年12月期间,在北京天坛医院招募了88例被认为患有胶质瘤的患者和10名健康志愿者,采集了他们术前6ml血液样本。采用减法富集(SE)-免疫荧光原位杂交(iFISH)技术捕获样本中的异倍体8号染色体细胞。同时,使用着丝粒探针8(CEP-8)-FISH技术鉴定10个肿瘤组织和10个脑组织中的非整倍体细胞。在肿瘤组织中观察到大量异倍体8号染色体细胞,而脑组织中结果为阴性(0.01)。90.9%的胶质瘤患者成功检测到循环肿瘤细胞,相比之下,只有1名健康志愿者检测到1个异倍体8号染色体细胞(0.01)。绝大多数循环肿瘤细胞(96.1%)未表现出胶质纤维酸性蛋白。无IDH突变的高级别胶质瘤(HGG)的循环肿瘤细胞比低级别胶质瘤多得多(12.0对2.2),P<0.01。此外,多倍体(≥5拷贝)循环肿瘤细胞在HGG中占比显著更高,无论是起源于少突胶质细胞还是星形胶质细胞的肿瘤(75.9%对56.0%),P<0.01;分别为62.7%对51.7%,P=0.016。通过检测血液中的非整倍体细胞可以在胶质瘤中识别和计数循环肿瘤细胞。循环肿瘤细胞的数量和多倍体比例可能与肿瘤分级和分子特征相关。

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