DNA methylation meningioma biomarkers: attributes and limitations

Li, Zhaohui; Gao, Yufei; Zhang, Jinnan; Han, Liang; Zhao, Hang

doi:10.3389/fnmol.2023.1182759

Cited by 8 publications

(3 citation statements)

References 88 publications

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“…At the individual CpG level, they identified 14 different CpGs within the CDKN2A gene locus that displayed a significant correlation with CDKN2A mRNA expression. Nevertheless, previous investigations have found that apart from being deleted, CDKN2A hypermethylation as an epigenetic silencing is linked to unfavorable outcomes [ 18 , 30 ]. Against this backdrop, it remains still unclear whether this hypermethylation serves as a regulatory mechanism contributing to increased expression or is merely a coincidental event within the broader context of elevated global methylation observed in aggressive meningiomas.…”

Section: Discussionmentioning

confidence: 99%

CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data

Wach,

Basaran,

Arlt

et al. 2023

acta neuropathol commun

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Homozygous CDKN2A/B deletion has been associated with an increased risk of recurrence in meningiomas. However, the evidence is confined to a limited number of studies, and the importance of heterozygous CDKN2A/B deletions remains insufficiently investigated. Hence, the present meta-analysis reconstructs individual patient data (IPD) and reconstructs the probabilities of progression-free survival (PFS) stratified by CDKN2A/B status. IPD of PFS rates were extracted from published Kaplan–Meier plots using the R package IPDfromKM in R studio (RStudio, Boston, MA, USA). Reconstructed Kaplan–Meier Plots of the pooled IPD data were created. One-stage and two-stage meta-analyses were performed. Hazard ratios (HR) were used as effective measures. Of 181 records screened, four articles with 2521 participants were included. The prevalence of homozygous CDKN2A/B deletions in the included studies was 0.049 (95% CI 0.040–0.057), with higher tumor grades associated with a significantly greater proportion of CDKN2A/B deletions. The reconstructed PFS curves for the pooled cohort showed that the median PFS time of patients with a CDKN2A/B wild-type status, heterozygous or homozygous CDKN2A/B deletion was 180.0 (95% CI 145.7–214.3), 26.1 (95% CI 23.3–29.0), and 11.00 (95% CI 8.6–13.3) months, respectively (p < 0.0001). Both hetero- or homozygous CDKN2A/B deletions were significantly associated with shortened time to meningioma progression. One-stage meta-analysis showed that hetero- (HR: 5.5, 95% CI 4.0–7.6, p < 0.00001) and homozygous CDKN2A/B deletions (HR: 8.4, 95% CI 6.4–11.0, p < 0.00001) are significantly associated with shortened time to meningioma progression. Multivariable Cox regression analysis of progression in a subgroup with available covariates (age, sex, WHO grade, and TERT status) and also two-stage meta-analysis confirmed and validated the results of the one-stage analysis that both heterozygous and homozygous CDKN2A/B deletions are of prognostic importance. Further large-scale studies of WHO grade 2 and 3 meningiomas are needed to validate the importance of heterozygous CDKN2A/B deletions with consideration of established factors.

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Section: Discussionmentioning

confidence: 99%

CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data

Wach,

Basaran,

Arlt

et al. 2023

acta neuropathol commun

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“…Some genetic alterations discovered in higher grade meningioma are deletions on 1p, 6q, 10q, 14q, 9p (CDKNA, p14 ARF , CDKN2B) and 18q chromosomes and gains on 1q, 9q, 12q, 15q, 17q, and 20q [77][78][79][80]82]. Several genes associated with oncogenesis of meningioma are: TRAF7, ATK1, KLF4, SMO, PIK3CA, BAP1, POLR2A, SMARCB1, AKT1E17K, hTERT/telomerase, MADH2, MADH4, APM-1, DCC, CDKN2A, p14 ARF , CDKN2B, TP53, MEG3, ALPL, Notch, WNT, IGF, NDRG2, TERT, H3K27me3, Cx43, SMARCE1, AKP12, ARID4B, DNA methylation and loss of heterozygosity of DAL1 [76,77,[79][80][81][82][83][84][85][86][87].…”

Section: Benign Tumorsmentioning

confidence: 99%

Advances in Mass Spectrometry of Gangliosides Expressed in Brain Cancers

Biricioiu,

Sarbu,

Ica

et al. 2023

Preprint

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Gangliosides are highly abundant in the human brain where they are involved in major biological events. In brain cancers, alterations of ganglioside pattern occur, some of which being correlated with the neoplastic transformation, while others with the tumor proliferation. Of all the techniques, mass spectrometry (MS) has proven to be one of the most effective in gangliosidomics, due to its ability to characterize heterogeneous mixtures and discover species with biomarker value. This review highlights the most significant achievements of MS in the analysis of gangliosides in human brain cancers. The first part presents the state-of-the-art in the MS development for discovery of ganglioside markers in primary brain tumors, with a particular emphasis on the ion mobility separation (IMS) MS and its contribution to the elucidation of the gangliosidome associated with aggressive tumors. The second part is focused on the MS of gangliosides in brain metastases, highlighting the ability of matrix-assisted laser desorption/ionization (MALDI)-MS, microfluidics-MS and tandem MS to decipher and structurally characterize species involved in the metastatic process. In the end, several conclusions and perspectives are presented, among which the need for development of a reliable software and a user-friendly structural database as a search platform in brain tumor diagnostics.

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“…These indicators can assist in identifying special protein and molecular-level pathways, classifying meningiomas into different subtypes, and developing real-time clinical biomarkers. [10][11][12] Neutrophils are inflammatory cells that secrete a variety of chemical mediators, including elastase and matrix metalloproteinase enzymes, along with growth factors. These mediators are well known for encouraging tumor growth and progression by developing a tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte Ratio as an Effective Biomarker for Meningioma: A Systematic Review and Meta-analysis

Khanzadeh,

Azarhomayoun,

Rahmati

et al. 2023

Explor Res Hypothesis Med

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Background and objectives: Previous studies showed that tumors are associated with the increased inflammatory burden and neutrophil-to-lymphocyte ratio (NLR) is also associated with inflammatory conditions. However, there is no review on the role of NLR in meningioma. The goal of this study was to see if NLR has any prognostic and diagnostic value in meningioma. Methods:The search was conducted on PubMed, Scopus, and Web of Science up to 3 August 2023. A total of 23 studies were included in the systematic review, of which 13 were included in the meta-analysis.Results: It was found that patients with high-grade meningioma had higher levels of NLR compared to those with low-grade meningioma (standardized mean difference [SMD] = 0.72, 95% confidence interval [CI]: 0.21-1.23, p = 0.006)]. In addition, we found that there was no difference between NLR levels of patients with meningioma and those with gliomas (SMD, −0.19, 95% CI: −0.47-0.10, p = 0.20). Also, higher levels of NLR were found in patients with meningioma compared with healthy controls (SMD = 0.56, 95% CI: 0.24-0.88, p = 0.01). Studies showed that an NLR > 2.4 differentiated high-grade and low-grade meningioma, an NLR > 2.74 differentiated high and low progression-free survival groups, and an NLR > 2.59 was associated with recurrence, with high sensitivity and specificity. However, the NLR did not predict postoperative pneumonia following meningioma resection. Because of the contradiction, our study did not clearly demonstrate the difference in NLR levels in meningioma and other pathologies, so more studies are needed on this subject.Conclusions: NLR had significant diagnostic and prognostic value in meningioma. In general, we inferred a strong link between systemic inflammation assessed by NLR and meningioma, based on elevated levels of NLR in patients with meningioma compared to healthy controls. In addition, NLR had significant predictive potential for the progression and recurrence of meningioma. The predictive potential increased when combined with other diagnostic tools such as fibrinogen level. NLR may guide clinical decision making as an inflammatory marker and its relationship to therapeutic efficacy.

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DNA methylation meningioma biomarkers: attributes and limitations

Cited by 8 publications

References 88 publications

CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data

CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data

Advances in Mass Spectrometry of Gangliosides Expressed in Brain Cancers

Neutrophil-to-lymphocyte Ratio as an Effective Biomarker for Meningioma: A Systematic Review and Meta-analysis

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