Cytoplasm protein GFAP magnetic beads construction and application as cell separation target for brain tumors

Journal of Nanobiotechnology

Yang Zhao¹  Yipeng Han¹  Jie Ma¹  Feng Jiang¹  Jiajia Wang¹  Jian Yang¹  Qinhua Wang¹  Baocheng Wang¹  Xunxiang Guo²  Kai Wang³  Xiaofei Liang³  Junping Ao³ 

[1] Department of Pediatric Neurosurgery, Shanghai Xin Hua Hospital Affiliated To Shanghai Jiaotong University, School of Medicine;Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University;State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine;

关键词: Circulating tumor cell;    Cytoplasm protein;    Liquid biopsy;    Tumor diagnosis;    Brain tumor;   

DOI  :  10.1186/s12951-020-00729-9

来源: DOAJ

【 摘 要 】

Abstract Background It is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. Results Our data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue. Conclusions The results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.

【 授权许可】

Unknown