Biomarkers in Brain Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 3870

Special Issue Editor


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Guest Editor
Department of Neurology, Heidelberg University Hospital, 69120 Heidelberg, Germany
Interests: glioma; targeted therapy; treatment resistance; tumor cell networks; liquid biopsy; single-cell analysis

Special Issue Information

Dear Colleagues,

In recent years there have been enormous advances in the molecular understanding and diagnostics of brain tumors that led to the inclusion of genetic profiles into the 5th edition of the WHO classification. For example, IDH mutations, 1p/19q codeletions and TP53/ATRX status became mandatory diagnostic and prognostic biomarkers in glioma. Methylation classification allows a refined machine-learning-assisted diagnosis. Furthermore, expression profiles were used to decipher the specific molecular subgroups, and RNA sequencing with single-cell resolution can be used to reveal the intratumoral heterogeneity of brain tumors.

Although molecular analysis options have been widely expanded in recent years and are available for clinical decision making, with results being discussed in tumor boards, there is still a gap between the present analytical techniques and routine clinical usage. Methylation of the methylguanine-O6-methyltransferase (MGMT) promoter predicts response to chemotherapy, particularly temozolomide. However, besides the long-known MGMT, stratifying molecular markers are limited. Especially for patients with malignant brain tumors, primary or acquired resistance towards established and experimental therapies are frequent, and biomarkers to guide decision-making to the most promising agents are needed.  

More recently, new innovative approaches such as liquid biopsies, advanced imaging biomarkers and single-cell resolution analyses emerged in the attempt to close this gap. In parallel, new targeted, immune and cell therapies have entered clinical trials, offering high potential for identifying successful biomarker–drug combinations and treatment stratification based on molecular profiles. This Special Issue will highlight the role of biomarkers in brain tumors, covering both preclinical and clinical research that advances our understanding of new molecular markers for treatment decision making in brain tumors.

Dr. Tobias Kessler
Guest Editor

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Keywords

  • targeted therapy
  • treatment resistance
  • MGMT
  • brain tumor
  • liquid biopsy
  • imaging biomarkers
  • single-cell analysis

Published Papers (2 papers)

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Research

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11 pages, 615 KiB  
Article
A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
by Julia Gilhodes, Adèle Meola, Bastien Cabarrou, Guillaume Peyraga, Caroline Dehais, Dominique Figarella-Branger, François Ducray, Claude-Alain Maurage, Delphine Loussouarn, Emmanuelle Uro-Coste, Elizabeth Cohen-Jonathan Moyal and POLA Network
Cancers 2023, 15(12), 3067; https://doi.org/10.3390/cancers15123067 - 6 Jun 2023
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Abstract
Background. IDH mutant and 1p/19q codeleted oligodendrogliomas are the gliomas associated with the best prognosis. However, despite their sensitivity to treatment, patient survival remains heterogeneous. We aimed to identify gene expressions associated with response to treatment from a national cohort of patients with [...] Read more.
Background. IDH mutant and 1p/19q codeleted oligodendrogliomas are the gliomas associated with the best prognosis. However, despite their sensitivity to treatment, patient survival remains heterogeneous. We aimed to identify gene expressions associated with response to treatment from a national cohort of patients with oligodendrogliomas, all treated with radiotherapy +/− chemotherapy. Methods. We extracted total RNA from frozen tumor samples and investigated enriched pathways using KEGG and Reactome databases. We applied a stability selection approach based on subsampling combined with the lasso-pcvl algorithm to identify genes associated with progression-free survival and calculate a risk score. Results. We included 68 patients with oligodendrogliomas treated with radiotherapy +/− chemotherapy. After filtering, 1697 genes were obtained, including 134 associated with progression-free survival: 35 with a better prognosis and 99 with a poorer one. Eight genes (ST3GAL6, QPCT, NQO1, EPHX1, CST3, S100A8, CHI3L1, and OSBPL3) whose risk score remained statistically significant after adjustment for prognostic factors in multivariate analysis were selected in more than 60% of cases were associated with shorter progression-free survival. Conclusions. We found an eight-gene signature associated with a higher risk of rapid relapse after treatment in patients with oligodendrogliomas. This finding could help clinicians identify patients who need more intensive treatment. Full article
(This article belongs to the Special Issue Biomarkers in Brain Tumors)
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Review

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22 pages, 3827 KiB  
Review
Head-To-Head Comparison of PET and Perfusion Weighted MRI Techniques to Distinguish Treatment Related Abnormalities from Tumor Progression in Glioma
by Dylan Henssen, Lars Leijten, Frederick J. A. Meijer, Anja van der Kolk, Anne I. J. Arens, Mark ter Laan, Robert J. Smeenk, Anja Gijtenbeek, Elsmarieke M. van de Giessen, Nelleke Tolboom, Daniela E. Oprea-Lager, Marion Smits and James Nagarajah
Cancers 2023, 15(9), 2631; https://doi.org/10.3390/cancers15092631 - 5 May 2023
Cited by 5 | Viewed by 1670
Abstract
The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more [...] Read more.
The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned [S-methyl-11C]methionine, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) and 6-[18F]-fluoro-3,4-dihydroxy-L-phenylalanine ([18F]FDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP. Full article
(This article belongs to the Special Issue Biomarkers in Brain Tumors)
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