miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma

Abstract

Malignant gliomas are lethal primary intracranial tumors. To date, little information on the role of deregulated genes in gliomas have been identified. As the involvement of miRNAs in the carcinogenesis is well known, we carried out a pilot study to identify, as potential biomarkers, differentially expressed microRNAs in blood samples of patients affected by glioma. We studied the miRNAs’ expression, by means of microarray and Real-Time PCR, in 30 blood samples from glioma patients and in 82 blood samples of patients suffering from: (a) various neurological disorders (n=30), (b) primary B-lymphoma of the Central Nervous System (PCNSL, n=36) and (c) secondary brain metastases (n=16). By quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR), we identified significantly increased levels of two candidate biomarkers, miR-15b and miR-21, in blood of patients affected by gliomas. ROC analysis of miR-15b biomarker levels allowed to differentiate patients with tumour from patients without glioma. Furthermore, combined expression analyses of miR15b and miR-21 distinguished between patients with and without glioma (90% sensitivity and 100% specificity). In addition, a decrement in the expression levels of miR-16 characterized glioblastomas compared to low grade and anaplastic gliomas. In conclusion, this pilot study suggest that it’s possible to identify the disease state by meaning miR-15b and miR-21 markers in blood, while miR-16 can be used to distinguish glioblastoma from other grade gliomas. They can potentially be used as biomarkers for non-invasive diagnosis of gliomas; further studies are mandatory to confirm our preliminary findings.

A comprehensive meta-analysis of circulation miRNAs in glioma as potential diagnostic biomarker

“…One other article was also excluded as it studied diagnostic accuracy of circulating miRNA between glioblastoma and low grade glioma rather than miRNA biomarker in tumour and normal control. Consequently, 16 publications met our inclusion criteria and were included in this meta-analysis for [ 21 – 33 ] [ 29 , 34 , 35 ] ( Fig 1A ) .…”

“…Seven publications reported a panel of several miRNAs as a diagnostic biomarker, while nine studies discussed a single miRNA candidate ( Table 1 ) . D’Urso et al, Manterola et al, Zhang et al and Zhi et al reported two study cohorts in each of their articles [ 22 , 32 – 34 ]. Articles by Wang et al and Huang et al included a subset of three studies [ 26 , 35 ].…”

“…Of the 16 studies analyzed ( Table 1 ), 5 publications [ 22 , 23 , 30 , 33 , 34 ] tested global miRNA expression using a panel of miRNA available commercially including those using the Taqman Low Density Array (TLDA) based on different versions of miRNA databases from mirBase [ 22 , 33 ]. Nine publications only focused on a targeted miRNA that has previously been assessed as potential biomarker or diagnostic marker in glioma or other cancer types ( Table 1 ).…”

“…Nine publications only focused on a targeted miRNA that has previously been assessed as potential biomarker or diagnostic marker in glioma or other cancer types ( Table 1 ). Some studies used healthy volunteers as their controls, while one study included patients with other neurological conditions as controls [ 34 ]. All studies collected biofluid at the time of glioma diagnosis or prior to operation, however some studies also included blood collected post-surgery.…”

Serum amyloid A1 in combination with integrin αVβ3 increases glioblastoma cells mobility and progression

“…Genetic and molecular variability in patients with GBM, however, causes different outcomes and resistance levels after therapy and can lead to severe relapse. Recently, noncoding RNA, omics studies, and proteomic analyses of GBM extracellular vesicles have been helpful in identifying additional associated biomarkers and potential treatment strategies for GBM (Ivo D'Urso et al ., ; Kros et al ., ; Touat et al ., ).…”