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Theranostics 2019; 9(18):5347-5358. doi:10.7150/thno.33114 This issue Cite

Research Paper

Evaluation of serum extracellular vesicles as noninvasive diagnostic markers of glioma

Huayi Wang^1,3,5, Dengzhi Jiang², Wenzhe Li^1,6, Xiang Xiang², Jun Zhao², Bin Yu⁴, Chen Wang^1,5, Zhaohui He^2✉, Ling Zhu^1,5✉, Yanlian Yang^1,5✉

1. CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
2. Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
3. Department of Chemistry, Tsinghua University, Beijing, 100084, China
4. Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
5. University of Chinese Academy of Sciences, 19 A Yuquan Rd, Shijingshan District, Beijing 100049, China
6. Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China

✉ Corresponding authors: Zhaohui He (geno_hecom), Ling Zhu (zhulcn), Yanlian Yang (yangylcn)

Abstract

Rationale: Glioma is the most common malignant primary brain tumor in the central nervous system (CNS). The lack of reliable noninvasive diagnostic and prognostic methods is one of the main reasons for the high mortality of glioma. Serum has become a useful biomarker for the diagnosis and prognosis prediction of glioma because extracellular vesicles (EVs) carry molecular components from their parental cells.

Methods: To detect EVs and perform molecular analysis of serum EVs, we established and optimized a microbead-assisted method based on flow cytometry and estimated the efficacy of EGFR protein expression and NLGN3 and PTTG1 mRNA in serum EVs from glioma patients (n=23) and healthy individuals (n=12). We evaluated the ability of EGFR⁺ EVs to differentiate high-grade and low-grade glioma patients and checked the correlation between EGFR in EVs and the ki-67 labeling index (LI) in the tumor tissue.

Results: We demonstrated that EGFR⁺ EVs are effective diagnostic and prognostic markers of glioma. The expression of EGFR in serum EVs can accurately differentiate high-grade and low-grade glioma patients, and EGFR in EVs positively correlates with ki-67 LI in the tumor tissue. We also showed the potential of NLGN3 and PTTG1 mRNA in EVs for detecting glioma patients.

Conclusions: We demonstrate that the protein expression of EGFR in serum EVs is an effective diagnostic marker of glioma. EGFR in EVs highly correlates with the malignancy of glioma. We also show the potential of NLGN3 and PTTG1 in EVs for detecting glioma. The optimized flow cytometry with the aid of microbead-based EV enrichment show its potential as a noninvasive method for the detection of glioma and will be beneficial to the management of glioma.

Keywords: extracellular vesicle, glioma, liquid biopsy, EGFR, NLGN3

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