High-Throughput Sequencing-Based Identification of Serum Exosomal Differential miRNAs in High-Grade Glioma and Intracranial Lymphoma

Author:

Wang Shun1,Xu Zhenkuan2,Zhang Chao3,Yu Rui2,Jiang Jun2ORCID,Wang Chengwei2,Qu Chuncheng2

Affiliation:

1. Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012 Shandong, China

2. Department of Neurosurgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, China

3. Department of Clinical Laboratory, The Ninth People’s Hospital of Qingdao, Qingdao, Shandong 266000, China

Abstract

Objective. At present, no effective noninvasive method is currently available for the differential diagnosis of high-grade glioma and intracranial lymphoma. In the present study, we aimed to screen microRNA (miRNA) markers in serum exosomes for differential diagnosis of high-grade glioma and intracranial lymphoma using high-throughput sequencing technology. Methods. Patients with intracranial lymphoma or high-grade glioma and healthy controls were included in this study (training cohort ( n = 10 ) and validation cohort: intracranial lymphoma ( n = 10 ), high-grade glioma ( n = 32 ), and healthy controls ( n = 20 )). After RNA was extracted from serum exosomes, the high-throughput sequencing was used to determine the expression profiles of serum exosomal miRNAs and screen the differentially expressed miRNAs. RT-qPCR was used to verify the expressions of the selected miRNAs. The differences of miRNA expressions between groups were assessed by the Kruskal-Wallis test. The diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. Results. High-throughput sequencing demonstrated that 170 miRNAs, including 109 upregulated ones and 61 downregulated ones, were differentially expressed in serum exosomes between the patients with intracranial lymphoma and high-grade glioma. Compared with the healthy controls, the number of differential serum exosomal miRNAs in the high-grade glioma group and intracranial lymphoma group was 130 and 173, respectively. RT-qPCR proved that both miR-766-5p and miR-376b-5p were significantly downregulated in high-grade glioma and intracranial lymphoma patients compared with the healthy controls (all p < 0.001 ), and the expression of serum exosomal miR-766-5p in the intracranial lymphoma group was lower compared with the high-grade glioma group ( p < 0.05 ). The areas under ROC curve (AUCs) of serum exosomal miR-766-5p and miR-376b-5p for the diagnosis of glioma were 0.8883 ( p < 0.001 ) and 0.7688 ( p = 0.001 ), respectively, and they were 0.9271 ( p < 0.001 ) and 0.8542 ( p < 0.001 ), respectively, for the diagnosis of intracranial lymphoma. Moreover, the AUC value of serum exosomal miR-766-5p for the differential diagnosis of glioma and intracranial lymphoma was 0.7201 ( p = 0.026 ). Conclusions. miR-766-5p and miR-376b-5p in serum exosomes might be used as auxiliary diagnostic indicators for high-grade glioma and intracranial lymphoma, and miR-766-5p might be used as a differential diagnostic marker for both diseases.

Funder

Natural Science Foundation of Shandong Province

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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