MicroRNAs in the Diagnosis of Malignancy of Supratentorial Brain Gliomas and Prognosis of Disease Progression

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Abstract

Introduction: The study of brain tumors has shown that microRNAs can act as both oncogenes and tumor suppressors and, consequently, can be used as biomarkers for the diagnosis and prognosis of such tumors. Thus, big interest arises in the role of microRNA and its part in oncogenesis in the human brain to find key molecules that can act as tumor markers for diagnostic and prognostic purposes, as well as potential therapeutic agents.

Study aim: The sim of this study was to assess histological, molecular, and genetic metrics in patients with supratentorial gliomas, and indicate diagnostic and prognostic abilities of microRNA usage as biomarkers of the grade of malignancy of the tumor.

Materials and methods: Clinical and genetic studies were performed in 107 operated patients with supratentorial gliomas of different malignancies. The expression levels of 10 microRNAs (-16, -21¸ -31, -124, - 125b, -181b, -191, -221, -223, and -451) were analyzed using real-time polymerase chain reaction (PCR). The results were analyzed statistically using Statistica 12.0 (Statistica, Hamburg, Germany) and GraphPad Prism 9 software (GraphPad Software Inc., Boston, Massachusetts, United States).

Results: Based on a comprehensive statistical analysis involving the database of the clinical results of treatment of all 107 patients (combined treatment methods, quality of life, and survival) and microRNA expression levels, specific profiles of microRNA expression typical of different histotypes of gliomas of different malignancy were identified, the prognostic significance of the studied microRNAs as potential predictors of survival in patients with brain gliomas was determined, and microRNAs with the highest prognostic value were identified among them.

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The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

Paul Kleihues, Otmar D. Wiestler, Guido Reifenberger … (2016)

The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.

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The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

David N Louis, Arie Perry, Pieter Wesseling … (2021)

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

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Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

Roger Stupp, Monika E Hegi, Warren P Mason … (2009)

In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 8 March 2023

Publication date (Electronic, collection): March 2023

Volume: 15

Issue: 3

Electronic Location Identifier: e35906

Affiliations

[1 ] Department of Neurosurgery, Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk, RUS

[2 ] Laboratory of Genetics, Institute of Molecular and Cell Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, RUS

[3 ] Genetics, AO Vector-Best, Novosibirsk, RUS

[4 ] Department of Psychiatry, Jamaica Hospital Medical Center, New York City, USA

[5 ] Department of Neurology, State University of New York Downstate Medical Center, New York City, USA

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Arsen S. Askandaryan askandaryanmd@ 123456gmail.com

Article

DOI: 10.7759/cureus.35906

PMC ID: 10081567

SO-VID: 6a3cac40-1cfc-4d4d-b593-12426fc17ece

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Date accepted : 8 March 2023

MicroRNAs in the Diagnosis of Malignancy of Supratentorial Brain Gliomas and Prognosis of Disease Progression

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Most cited references 30

The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

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