Abstract

This study investigated whether antibody-modified immunomagnetic microspheres (IMs) can be used to detect and quantify circulating tumor cells (CTCs) originating from gliomas in liquid biopsies and whether CTC counts in clinical samples are related to the degree of malignancy of gliomas based on clinical data. Epidermal growth factor receptor (EGFR)-antibody-modified and epithelial cell adhesion molecule (EpCAM)-modified IMs were developed, their physical properties, including particle size and zeta potential as well as their biocompatibility, were characterized, and their ability to detect CTCs originating from gliomas was evaluated using a mouse xenograft model and clinical specimens [cerebrospinal fluid (CSF) and peripheral blood collected from 30 patients with gliomas]. The results showed that EGFR-IMs and EpCAM-IMs had low cytotoxicity and that they could capture CTCs in mouse and human biofluids with high capture efficiency. Moreover, CTC counts in the human CSF were positively correlated with glioma grade. Thus, EGFR-IMs and EpCAM-IMs have clinical applicability for the diagnosis of glioma and for monitoring treatment response in patients.

Highlights

  • Gliomas are the most common intracranial primary malignant tumors in adults, with an annual incidence rate of about 10/100 000; the glioblastoma multiforme (GBM) subtype has the worst prognosis

  • For Epidermal growth factor receptor (EGFR)-immunomagnetic microspheres (IMs), the latter represented a statistically significant difference compared to earlier tumor stages. These results indicate that the number of Circulating tumor cells (CTCs) released into peripheral blood gradually increases with tumor development and that the cells can be detected by EGFR-IMs

  • epithelial cell adhesion molecule (EpCAM) is highly expressed in most epithelial tumor cells; EGFR is highly expressed on the surface of some glioma cells, and its overexpression and mutation are closely associated with tumor occurrence and development

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Summary

Introduction

Gliomas are the most common intracranial primary malignant tumors in adults, with an annual incidence rate of about 10/100 000; the glioblastoma multiforme (GBM) subtype has the worst prognosis. There is, a need for biomarkers that can be used for early diagnosis of glioma as well as for monitoring treatment response and evaluating prognosis in patients. Liquid biopsy is a relatively new diagnostic approach for tumors that allows for dynamic monitoring of changes (e.g., in gene expression) in the tumor. It can guide targeted drug therapy and predict treatment efficacy and is expected to replace surgery or puncture biopsy in the future. Circulating tumor cells (CTCs) have been detected in the peripheral blood of patients with primary brain tumors at a rate of 20%–70%.7. An effective and highly sensitive approach for detecting CTCs of brain tumors is, needed

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