Abstract 5396: Identification of meningioma patients in high risk of tumor recurrence using microRNA profiling

Abstract

Abstract Introduction: Meningioma represents one of the most common intracranial tumors. They are generally thought to progress from low to high-grade lesions and relapse. However, the molecular mechanisms underlying their pathogenesis remains to be ellucidated. Identification of meningioma patients with higher risk of recurrence may have significant impact for future clinical management. Methods and patients: Formalin-fixed paraffin embedded tumor samples were obtained from 45 meningioma patients (15 recurrent patients, 30 patients without recurrence) and 5 healthy controls (dura mater). Comprehensive clinical-pathological data were mined. There were 15 males and 30 females; median age was 54 years, range 28 - 99 years. Total RNA was purified from FFPE samples after pathological verification using miRNeasyMini kit (QIAGEN). Microarray analysis was performed using the MiRNA 4.0 Array and FlashTagTM Biotin HSR(Affymetrix). Affymetrix CEL files have been read with read.celfiles function from oligo package and preprocessed with rma function (Bioconductor). The expression dataset was analyzed with Wilcoxon exact two-sample test (exactRankTestsR package) in order to discover significantly altered miRNAs. Results: We revealed different miRNA profiles in primary meningioma tumors that will relapse in comparison with non-recurrent tumors. 54 differentially expressed miRNAs were identified in meningeoma patients at high risk of recurrence. High-risk patients had significantly higher expression of miR-572 and miR-320c, and lower expression of miR-140 and miR-16-5p. Sixteen candidate miRNAs (including miR-107, miR-16-5p, miR-320c, miR-371b-5p and miR-15a-5p) were chosen for further qPCR validation on independent dataset. Moreover, miRNA expression levels were also compared in paired samples (primary and recurrent tumors) of 15 meningioma patients. However, only small differences in miRNA expression were detected. Conclusion: We have found different miRNA profiles in meningioma patients identifying patients in high risk of recurrence. Sixteen candidate miRNAs (including miR-107, miR-16-5p, miR-320c, miR-371b-5p and miR-15a-5p) were further validated. Acknowledgment: This work was financially supported by Ministry of Health of the Czech Republic, grant nr. 15-29021A, IGA UP LF 2017_013, NPU LO1304 and NCMG LM2015091. Citation Format: Josef Srovnal, Vladimir Balik, Hanus Slavik, Magdalena Houdova Megova, Miroslav Vaverka, Lumir Hrabalek, Jiri Ehrmann, Katerina Staffova, Marian Hajduch. Identification of meningioma patients in high risk of tumor recurrence using microRNA profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5396.