BACKGROUND AND OBJECTIVES: Meningioma, the most common primary intracranial tumor, presents challenges in surgical treatment because of varying tissue stiffness. This study explores the molecular background of meningioma stiffness, a critical factor in surgical planning and prognosis, focusing on the utility of microRNAs (miRNAs) as diagnostic biomarkers of tissue stiffness. METHODS: Patients with meningiomas treated surgically at the University Hospital Brno were included in this study. Total RNA, isolated from tumor tissue samples, underwent quality control and small RNA sequencing to analyze miRNA expression. Differentially expressed miRNAs were identified, and their association with tumor stiffness was assessed. RESULTS: This study identified specific miRNAs differentially expressed in meningiomas with different stiffness levels. Key miRNAs, such as miR-31-5p and miR-34b-5p, showed significant upregulation in stiffer meningiomas. These findings were validated using reverse transcription-quantitative polymerase chain reaction, revealing a potential link between miRNA expression and tumor consistency. The expression of miR-31-5p was most notably associated with the stiffness of the tumor tissue (sensitivity = 71% and specificity = 83%). CONCLUSION: This research highlights the potential of miRNAs as biomarkers for determining meningioma tissue stiffness. Identifying specific miRNAs associated with tumor consistency could improve preoperative planning and patient prognosis. These findings pave the way for further exploration of miRNAs in the clinical assessment of meningiomas.

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Anesthesiology Resuscitation and Intensive Care University Hospital Brno Brno Czech Republic

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Biophysics Faculty of Medicine Masaryk University Brno Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Neurosurgery University Hospital Brno Brno Czech Republic

Department of Pathology University Hospital Brno Brno Czech Republic

Department of Radiology and Nuclear Medicine Faculty of Medicine Masaryk University Brno and University Hospital Brno Brno Czech Republic

Zobrazit více v PubMed

Holleczek B, Zampella D, Urbschat S, et al. Incidence, mortality and outcome of meningiomas: a population-based study from Germany. Cancer Epidemiol. 2019;62:101562. PubMed

Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020. Neuro Oncol. 2023;25(Supplement_4):iv1-iv99. PubMed PMC

Buerki RA, Horbinski CM, Kruser T, Horowitz PM, James CD, Lukas RV. An overview of meningiomas. Future Oncol. 2018;14(21):2161-2177. PubMed PMC

Ogasawara C, Philbrick BD, Adamson DC. Meningioma: a review of epidemiology, pathology, diagnosis, treatment, and future directions. Biomedicines. 2021;9(3):319. PubMed PMC

Maggio I, Franceschi E, Tosoni A, et al. Meningioma: not always a benign tumor. A review of advances in the treatment of meningiomas. CNS Oncol. 2021;10(2):CNS72. PubMed PMC

Ahmeti H, Borzikowsky C, Hollander D, et al. Risks and neurological benefits of meningioma surgery in elderly patients compared to young patients. J Neurooncol. 2021;154(3):335-344. PubMed PMC

Murphy MC, Huston J, 3rd, Glaser KJ, et al. Preoperative assessment of meningioma stiffness using magnetic resonance elastography. J Neurosurg. 2013;118(3):643-648. PubMed PMC

Sauvigny T, Ricklefs FL, Hoffmann L, Schwarz R, Westphal M, Schmidt NO. Features of tumor texture influence surgery and outcome in intracranial meningioma. Neurooncol Adv. 2020;2(1):vdaa113. PubMed PMC

Sumkovski R, Micunovic M, Kocevski I, Ilievski B, Petrov I. Surgical treatment of meningiomas - outcome associated with type of resection, recurrence, Karnofsky performance score, mitotic count. Open Access Maced J Med Sci. 2019;7(1):56-64. PubMed PMC

Dalan AB, Gulluoglu S, Tuysuz EC, et al. Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: a relationship between PTX3 and miR-29c. BMC Cancer. 2017;17(1):207. PubMed PMC

El-Gewely MR, Andreassen M, Walquist M, et al. Differentially expressed MicroRNAs in meningiomas Grades I and II suggest shared biomarkers with malignant tumors. Cancers (Basel). 2016;8(3):31. PubMed PMC

Saydam O, Shen Y, Wurdinger T, et al. Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. Mol Cell Biol. 2009;29(21):5923-5940. PubMed PMC

Shi L, Jiang D, Sun G, et al. miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas. J Neurooncol. 2012;110(2):155-162. PubMed

Zhi F, Zhou G, Wang S, et al. A microRNA expression signature predicts meningioma recurrence. Int J Cancer. 2013;132(1):128-136. PubMed

Wang M, Deng X, Ying Q, Jin T, Li M, Liang C. MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma. Biochem Biophys Res Commun. 2015;460(2):354-361. PubMed

Carneiro V, Cirino M, Panepucci R, et al. The role of microRNA 181d as a possible biomarker associated with tumor progression in meningiomas. Cureus. 2021;13(10):e19158. PubMed PMC

Li P, Gao Y, Li F, et al. MicroRNA-18a regulates invasive meningiomas via hypoxia-inducible factor-1α. Exp Ther Med. 2015;10(3):1165-1170. PubMed PMC

Kopkova A, Sana J, Machackova T, et al. Cerebrospinal fluid microRNA signatures as diagnostic biomarkers in brain tumors. Cancers (Basel). 2019;11(10):1546. PubMed PMC

Zhi F, Shao N, Li B, et al. A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma. Sci Rep. 2016;6:32067. PubMed PMC

NextSeq system denature and dilute libraries guide. Accessed 25 August 2018. {L-End} https://support.illumina.com/downloads/nextseq-500-denaturing-diluting-libraries-15048776.html

Andrews S. FastQC: a quality control tool for high throughput sequence data. Accessed August 25, 2018. {L-End} http://www.bioinformatics.babraham.ac.uk/projects/fastqc

Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 2011;17(1):10-12.

Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34(Database issue):D140-D144. PubMed PMC

Pantano L, Estivill X, Marti E. SeqBuster, a bioinformatic tool for the processing and analysis of small RNAs datasets, reveals ubiquitous miRNA modifications in human embryonic cells. Nucleic Acids Res. 2010;38(5):e34. PubMed PMC

Ewels P, Magnusson M, Lundin S, Kaller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32(19):3047-3048. PubMed PMC

Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. PubMed PMC

Smith KA, Leever JD, Chamoun RB. Predicting consistency of meningioma by magnetic resonance imaging. J Neurol Surg B Skull Base. 2015;76(3):225-229. PubMed PMC

Yao A, Pain M, Balchandani P, Shrivastava RK. Can MRI predict meningioma consistency?: a correlation with tumor pathology and systematic review. Neurosurg Rev. 2018;41(3):745-753. PubMed PMC

Zhai Y, Song D, Yang F, et al. Preoperative prediction of meningioma consistency via machine learning-based radiomics. Front Oncol. 2021;11:657288. PubMed PMC

Zhao D, Zhao X, Liu T, et al. Genetic alterations in meningiomas of different textures. Gene. 2016;592(1):134-139. PubMed

Doleshal M, Magotra AA, Choudhury B, Cannon BD, Labourier E, Szafranska AE. Evaluation and validation of total RNA extraction methods for microRNA expression analyses in formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2008;10(3):203-211. PubMed PMC

Kopkova A, Sana J, Fadrus P, Slaby O. Cerebrospinal fluid microRNAs as diagnostic biomarkers in brain tumors. Clin Chem Lab Med. 2018;56(6):869-879. PubMed

Pacifici M, Delbue S, Kadri F, Peruzzi F. Cerebrospinal fluid MicroRNA profiling using quantitative real time PCR. J Vis Exp. 2014;83:e51172. PubMed PMC

Saugstad JA, Lusardi TA, Van Keuren-Jensen KR, et al. Analysis of extracellular RNA in cerebrospinal fluid. J Extracell Vesicles. 2017;6(1):1317577. PubMed PMC

Slavik H, Balik V, Vrbkova J, et al. Identification of meningioma patients at high risk of tumor recurrence using microRNA profiling. Neurosurgery. 2020;87(5):1055-1063. PubMed PMC

Wang L, Chen S, Liu Y, et al. The biological and diagnostic roles of MicroRNAs in meningiomas. Rev Neurosci. 2020;31(7):771-778. PubMed

Marigliano C, Badia S, Bellini D, et al. Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression. Technol Cancer Res Treat. 2019;18:1533033819878458. PubMed PMC

Li B, Liu J, Xin X, et al. MiR-34c promotes hepatic stellate cell activation and Liver Fibrogenesis by suppressing ACSL1 expression. Int J Med Sci. 2021;18(3):615-625. PubMed PMC

Li F, Ma N, Zhao R, et al. Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice. J Cell Mol Med. 2014;18(6):966-974. PubMed PMC

Ma J, Liu Q, Chen M, et al. MicroRNA-34b-5p binds enhancer of zeste 2 to inhibit milk fat globule-EGF factor 8 expression, affecting liver fibrosis. J Physiol Biochem. 2022;78(4):885-895. PubMed

Morizane R, Fujii S, Monkawa T, et al. miR-34c attenuates epithelial-mesenchymal transition and kidney fibrosis with ureteral obstruction. Sci Rep. 2014;4:4578. PubMed PMC

Niture S, Gadi S, Qi Q, et al. MicroRNA-483-5p inhibits hepatocellular carcinoma cell proliferation, cell steatosis, and fibrosis by targeting PPARα and TIMP2. Cancers (Basel). 2023;15(6):1715. PubMed PMC

Piccolo P, Ferriero R, Barbato A, et al. Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis. Proc Natl Acad Sci U S A. 2021;118(10):e2025242118. PubMed PMC

Bai X, Zheng L, Xu Y, Liang Y, Li D. Role of microRNA-34b-5p in cancer and injury: how does it work? Cancer Cell Int. 2022;22(1):381. PubMed PMC

Kim JS, Kim EJ, Lee S, et al. MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas. Exp Mol Med. 2019;51(1):1-10. PubMed PMC

Wang N, Li Y, Zhou J. miR-31 functions as an oncomir which promotes epithelial-mesenchymal transition via regulating BAP1 in cervical cancer. Biomed Res Int. 2017;2017:6361420. PubMed PMC

Yang J, Liu X, Sun Y, et al. ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells. Acta Biochim Biophys Sin (Shanghai). 2023;55(5):809-817. PubMed PMC

Yu T, Ma P, Wu D, Shu Y, Gao W. Functions and mechanisms of microRNA-31 in human cancers. Biomed Pharmacother. 2018;108:1162-1169. PubMed