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Exosomal microRNA-210 is a potentially non-invasive biomarker for the diagnosis and prognosis of glioma.

ABSTRACT: MicroRNAs (miRs) transferred by exosomes can function as non-invasive potential biomarkers for the diagnosis and prognosis in various types of cancer. The present study examined the diagnostic and prognostic value of serum exosomal-(exo-)miR-210 levels in association with hypoxic conditions in patients with glioma. Serum levels of exo-miR-210 were determined by quantitative PCR in samples obtained from patients with glioma. Patients were divided into low-and high-expression exo-miR-210 groups according to the median expression value. Statistical analyses were conducted to examine the potential value of exo-miR-210 in predicting the diagnosis and prognosis of patients with glioma. A significant increase in serum exo-miR-210 levels was observed in patients with glioma compared with healthy controls. Additionally, the expression levels of exo-miR-210 were increased with ascending pathological grades. Furthermore, expression levels of miR-210 in serum exosomes from patients with glioblastoma were markedly decreased following surgery and upregulated once more at the recurrences of primary tumors, indicating that exo-miR-210 could reflect alterations in malignant glioma loads. In addition, Kaplan-Meier analysis was performed to analyze overall survival (OS) time. Patients with malignant glioma with high exo-miR-210 expression exhibited a poorer OS compared with patients with low expression. Importantly, univariate and multivariate Cox regression analysis revealed that the expression levels of exo-miR-210 in glioma serum samples were independently associated with OS. Finally, increased serum exo-miR-210 expression was positively associated with high levels of hypoxia-inducible factor 1a and reflected hypoxia in patients with glioma. In conclusion, serum levels of exo-miR-210 may serve as a diagnostic, prognostic and hypoxic biomarker to reflect glioma status and hypoxic signatures.

SUBMITTER: Lan F

PROVIDER: S-EPMC7039075 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Exosomal microRNA-210 is a potentially non-invasive biomarker for the diagnosis and prognosis of glioma.

Lan Fengming F Yue Xiao X Xia Tingyi T

Oncology letters 20200107 3

MicroRNAs (miRs) transferred by exosomes can function as non-invasive potential biomarkers for the diagnosis and prognosis in various types of cancer. The present study examined the diagnostic and prognostic value of serum exosomal-(exo-)miR-210 levels in association with hypoxic conditions in patients with glioma. Serum levels of exo-miR-210 were determined by quantitative PCR in samples obtained from patients with glioma. Patients were divided into low-and high-expression exo-miR-210 groups ac ...[more]

PMID: 32194691

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Project description:Background: Safe and sensitive methods for glioblastoma diagnosis and disease monitoring are urgently needed. Exosomes are nano-sized extracellular vesicles that contain molecules characteristic of their cell-of-origin, including microRNA. Exosomes released by glioblastoma tumors cross the blood-brain-barrier ino the peripheral circulation. Methods: Serum exosomal-microRNA isolated from IDH-wildtype glioblastoma (n=12) and IDH-mutant glioma grades II-III (n=10) were analyzed using small-RNA next generation sequencing and compared to age- and gender-matched healthy controls. Differentially expressed miRNAs (|fold change|³2 and p-value ≤ 0.05 in three statistical tests, Fischer-exact, t-test, and Wilcoxon) were identified and the predictive power of individual and subsets of miRNAs were tested using univariate (logistic regression) and multivariate (Random Forest) analyses. Additional glioblastoma sera (n=4) and independent sets of healthy (n=9) and non-glioma (n=10) controls were used to further test the predictive power of our glioblastoma miRNA signature. Results: Twenty-six miRNAs were differentially expressed in glioblastoma relative to healthy controls. Seven miRNAs (miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p and miR-543) were the most stable for classifying glioblastoma, achieving a predictive power of 91.7%. Strikingly, the combined expressions of miR-182-5p, miR-328-3p miR-485-3p miR-486-5p distinguished glioblastoma patients from controls with perfect accuracy. This miRNA panel was able to correctly classify all specimens in validation cohorts (n=23). An analogous approach was used to identify 23 dysregulated miRNAs in IDH-mutant gliomas, including a distinct subset of stable miRNAs for classifying patients with lower-grade IDH-mutant gliomas. Conclusions: Our serum exosomal-miRNA signature can accurately diagnose glioblastoma preoperatively. These findings have significant scope to revolutionize glioblastoma tumor diagnosis and disease monitoring. IMPORTANCE OF STUDY: There is a real need for accurate biomarkers that can measure glioblastoma disease activity and treatment response in a safe and timely manner. This study demonstrates that exosome-associated microRNAs have exceptional utility as blood-based biomarkers in glioma patients. This work also shows the potential for exosomal microRNA profiles to be used for glioma subtyping, grading and determining mutational states. The development of specific, sensitive and non-invasive screening tests would have significant clinical benefit by reducing costs of treatment monitoring, improving accessibility and quality-of-life measures. Moreover, such tests have the potential to provide objectively measured surrogate endpoints to allow clinical trial protocols to be more dynamic and adaptive.

Dataset Information

Exosomal microRNA-210 is a potentially non-invasive biomarker for the diagnosis and prognosis of glioma.

Publications

Exosomal microRNA-210 is a potentially non-invasive biomarker for the diagnosis and prognosis of glioma.

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