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

الملخص EN

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.