Expression-based decision tree model reveals distinct microRNA expression pattern in pediatric neuronal and mixed neuronal-glial tumors

Abstract

Background The understanding of the molecular biology of pediatric neuronal and mixed neuronal-glial brain tumors is still insufficient due to low frequency and heterogeneity of those lesions which comprise several subtypes presenting neuronal and/or neuronal-glial differentiation. Important is that the most frequent ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) showed limited number of detectable molecular alterations. In such cases analyses of additional genomic mechanisms seem to be the most promising. The aim of the study was to evaluate microRNA (miRNA) profiles in GGs, DNETs and pilocytic asytrocytomas (PA) and test the hypothesis of plausible miRNA connection with histopathological subtypes of particular pediatric glial and mixed glioneronal tumors. Methods The study was designed as the two-stage analysis. Microarray testing was performed with the use of the miRCURY LNA microRNA Array technology in 51 cases. Validation set comprised 107 samples used during confirmation of the profiling results by qPCR bioinformatic analysis. Results Microarray data was compared between the groups using an analysis of variance with the Benjamini-Hochberg procedure used to estimate false discovery rates. After filtration 782 miRNAs were eligible for further analysis. Based on the results of 10 × 10-fold cross-validation J48 algorithm was identified as the most resilient to overfitting. Pairwise comparison showed the DNETs to be the most divergent with the largest number of miRNAs differing from either of the two comparative groups. Validation of array analysis was performed for miRNAs used in the classification model: miR-155-5p, miR-4754, miR-4530, miR-628-3p, let-7b-3p, miR-4758-3p, miRPlus-A1086 and miR-891a-5p. Model developed on their expression measured by qPCR showed weighted AUC of 0.97 (95% CI for all classes ranging from 0.91 to 1.00). A computational analysis was used to identify mRNA targets for final set of selected miRNAs using miRWalk database. Among genomic targets of selected molecules ZBTB20 , LCOR , PFKFB2 , SYNJ2BP and TPD52 genes were noted. Conclusions Our data showed the existence of miRNAs which expression is specific for different histological types of tumors. miRNA expression analysis may be useful in in-depth molecular diagnostic process of the tumors and could elucidate their origins and molecular background. Electronic supplementary material The online version of this article (10.1186/s12885-019-5739-5) contains supplementary material, which is available to authorized users.

PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma

“…In our study, we present a statistical correlation between miR-155 and PD-L1 in a small homogeneous group of patients with a rare malignant tumor, namely, p-HGG. The results presented correspond with the thesis that miR-155 has a strong impact on PD-L1 expression and that both are correlated with unfavorable outcomes [37,38]. All previous studies were performed on adult glioblastoma groups of patients or performed on cell lines.…”

Association between DNA methylation levels in brain tissue and late-life depression in community-based participants

“…At last, previous studies suggest that YOD1 contributes to pathogenesis of neurodegenerative disease like Huntington disease and Parkinson's disease 30 . PFKFB2 has been studied in the context of brain tumors 36,37 , but there is no evidence for an association with neuropsychological disease. Therefore, we hypothesize that the CpG sites we found to be associated with late-life MDD are most likely linked to YOD1 regulation.…”

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

“…After induced middle cerebral artery ischemic stroke in rats, Li et al ascertained that let-7b-3p had a low expression in both blood and penumbra brain tissue, whereas another microRNA, namely miR-223-3p, had an increased level both in serum and ischemic penumbra [123]. Moreover, let-7b-3p is believed to possess a tumor repressing ability in gliomas, its decreased expression being correlated to a poorer prognosis in patients with these lesions via a disturbed suppression of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), E2F2, and the oncogenes KRAS, HMGA2 and MYC [124][125][126]. Findings such as these may highlight that BAVMs and CCMs have distinct pathological cascades that potentially converge at a crossroad, the only difference being the over-or underexpression of a certain microRNA such as let-7b-3p.…”