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.
Highlights
High-grade glioma and intracranial lymphoma are all highly proliferative and aggressive tumors with a poor prognosis and short survival
Compared with the normal controls, there were 130 differential miRNAs in the high-grade glioma group and 173 differential miRNAs in the intracranial lymphoma group. miR-122-5p, miR-1301-3p, miR-194-5p, miR-370-3p, miR-328-3p, miR-181a-5p, miR-191-5p, miR328-3p, miR-133a-3p, miR-494-3p, miR-331-5p, miR-5325p, miR-370-3p, let-7c-5p, miR-766-5p, and so on were differentially expressed in serum exosomes of the high-grade glioma group compared with the intracranial lymphoma group, and they were all differentially expressed in serum exosomes of the high-grade glioma group and intracranial lymphoma group compared with the normal controls
Our study screened out two miRNAs in serum exosomes, which were related to the diagnosis of high-grade glioma and intracranial lymphoma
Summary
High-grade glioma and intracranial lymphoma are all highly proliferative and aggressive tumors with a poor prognosis and short survival. It is difficult or even impossible to distinguish high-grade glioma and intracranial lymphoma due to the similarity of their appearance on the conventional CT and MRI examinations [1]. BioMed Research International to distinguish intracranial lymphoma and high-grade glioma, while many patients cannot accept such invasive examination approach. It is very necessary to differentiate them, because the therapeutic methods of them are quite different. Intracranial lymphoma is more sensitive to chemotherapy and radiation [2]. It is urgently necessary to identify an efficient and noninvasive detection indicator for the differential diagnosis of both diseases
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