miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas

Abstract

In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma.

Prognostic relevance of miR‐124‐3p and its target TP53INP1 in pediatric ependymoma

“…Costa et al identified over expression of miR‐203 as an independent marker for relapse . In a recent study, miR‐15a and miR‐24‐1 were found upregulated in ependymoma associated with inferior prognosis . These miRs were not identified in our study.…”

“…12 In a recent study, miR-15a and miR-24-1 were found upregulated in ependymoma associated with inferior prognosis. 13 These miRs were not identified in our study. This may be due to the difference in the comparison groups.…”

“…Alterations in miR expression levels have been detected in many types of human cancers . Despite the limited information available, a number of miR alterations have been identified in ependymoma that correlate with survival …”

“…10 Despite the limited information available, a number of miR alterations have been identified in ependymoma that correlate with survival. [11][12][13] As miR expression has proven to play an important role in malignancies and has emerged as a powerful tool in identifying candidate genes involved in their biology, we initiated a study in an attempt to identify miRs and their target genes in pediatric ependymoma. We collected demographic information including patient age, gender, location of the tumor (supra or infratentorial and spinal), tumor grade as noted by the pathologist (there was no central review), extent of resection, adjuvant radiation, recurrence, and survival status.…”

Investigation of miRNA and mRNA Co-expression Network in Ependymoma

“…Thus, identification of miRNA-mRNA pairs and discovering the regulation network may potentially uncover useful cancer biomarkers. Recent research has revealed miR-15a and miR-24-1 are up-regulated in EPNs relapsed and deceased cases when compared to both the clinical remission cases and survivors, and may serve as a candidate of inferior prognostic molecules in children with EPNs (Braoudaki et al, 2016). As important regulators of life activities, miRNAs are closely related to cancer (Hayes et al, 2014) through its altered expression levels that affect the content of downstream genes (Esquela-Kerscher and Slack, 2006).…”