A restricted signature of serum miRNAs distinguishes glioblastoma from lower grade gliomas

Abstract

Background: Malignant gliomas are the most common primary brain tumors in adults and challenging cancers for diagnosis and treatment. They remain a disease for which non-invasive, diagnostic and/or prognostic novel biomarkers are highly desirable. Altered microRNA (miRNA) profiles have been observed in tumor tissues and biological fluids. To date only a small set of circulating/serum miRNA is found to be differentially expressed in brain tumors compared to normal controls. Here a restricted signature of circulating/serum miRNA including miR-15b*,-23a, −99a, −125b, −133a, −150*, −197, −340, −497, −548b-5p and let-7c were investigated as potential non-invasive biomarkers in the diagnosis of glioma patients. Methods: Serum and tissues miRNAs expression in patients with brain cancers (n = 30) and healthy controls (n = 15) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative expression was calculated using the comparative Ct method. Statistical significance (p ≤ 0,05) was determined using the Mann-Whitney rank sum and Fisher's exact test. Diagnostic accuracy of miRNAs in distinguishing glioblastoma multiforme (GBM) from lower grade cancer was assessed by the Receiver Operating Characteristic (ROC) curve analysis. To validate the role of the identified miRNAs in cancer a comprehensive literature search was conducted using PubMed, Web of Science (Core Collection) and Scopus databases.

MicroRNAs as potential biomarkers for the diagnosis of glioma: A systematic review and meta‐analysis

“…Subsequently, we assessed the remaining 254 full‐text articles and excluded 226 studies based on the exclusion criteria, including 30 meetings, and 196 without clinical data to make a 2 × 2 contingency table. In total, 28 studies were ultimately included in this study . A flowchart of the selection process for this study is presented in Figure .…”

“…4 Thus, finding useful molecular markers to guide clinicians in optimizing treatment of glioma patients is important. miRNAs are a class of small non-coding RNA with [19][20][21][22] nucleotides. miRNAs have been found to be closely related to cancers because of the alterations in target binding sites of miRNAs and the miRNA processing machinery in tumor cells.…”

Circulating microRNAs as emerging non-invasive biomarkers for gliomas

“…Notably, serum levels of miR-210 did not differ from those in healthy controls in the study by Siegal and colleagues (21). The possibility to distinguish high grade from low grade gliomas was proposed also by the expression of serum miR-497 and miR-125b (19) and miR-29 (33), which were all downregulated in GBM IV (19). miRNAs could be used as a disease follow-up marker as demonstrated by decreased levels of serum miR-21 after surgical tumor resection (17,33) or by persistently high expression associated with tumor progression (33).…”

“…As shown in Figure 1, miR-21 (which is known to be overexpressed in GBM IV tissue) was found to be elevated also in serum exosomes from patients with GBM IV (17). Other examples of circulating miRNAs as mirrors of tissue miRNA level in gliomas are miR-497 and miR-125b that have been described to be downregulated both in serum and tissue tumors of patients with GBM IV (19). Unlike these biomarkers, no correlation between blood and tissue expression levels was reported for miR-128, which was found significantly increased in blood of GBM IV patients and down-regulated in GBM IV tissue (20).…”

The role of micro-RNA in the regulation of signal pathways in gliomas

“…При этом пациенты с глиобластомой имеют достоверно сниженный уровень экспрессии miR-497 и miR-125b, чем пациенты с глиомами низкой степени злокаченности [125]. MiR-210 в сыворотке крови также является перспективным диагностическим и прогностическим биомаркером, который может определяться в периферической крови пациентов с глиомами, поскольку уровень miR-210 в сыворотке при глиобластоме примерно в 7 раз выше по сравнению со здоровыми донорами [126].…”