Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma
| Autor: | Krzysztof Zakrzewski, Magdalena Zakrzewska, Wiesława Grajkowska, Iwona Filipek, Beata Sikorska, Łukasz Stefańczyk, Bożenna Dembowska-Bagińska, Pawel P. Liberski, Wojciech Fendler |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Ependymoma Pathology Multivariate analysis lcsh:Medicine Artificial Gene Amplification and Extension Infratentorial Neoplasms Biochemistry Polymerase Chain Reaction Pediatrics Negative Staining Medicine and Health Sciences Pediatric ependymoma Child lcsh:Science Neurological Tumors Staining Multidisciplinary Brain Neoplasms Immunohistochemistry Nucleic acids Gene Expression Regulation Neoplastic Survival Rate Oncology Neurology Child Preschool Infratentorial Neoplasm Epigenetics Female Research Article medicine.medical_specialty DNA Complementary Adolescent Biology Research and Analysis Methods Disease-Free Survival 03 medical and health sciences Genetics Biomarkers Tumor Childhood Infratentorial Ependymoma medicine Humans Non-coding RNA Molecular Biology Techniques Molecular Biology Cytoplasmic Staining Survival rate Survival analysis Biology and life sciences lcsh:R Cancers and Neoplasms Infant medicine.disease Gene regulation MicroRNAs 030104 developmental biology Specimen Preparation and Treatment RNA lcsh:Q Gene expression |
| Zdroj: | PLoS ONE, Vol 11, Iss 7, p e0158464 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors. Methods The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR. Results Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses. Conclusions Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome. |
| Databáze: | OpenAIRE |
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