Molecular Biomarkers in Glioblastoma: A Systematic Review and Meta-Analysis

Abstract

Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients. Material and methods: A comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients. Results: Twenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32–2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81–3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96–1.79; p = 0.08). Conclusions: MGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.

Exploring Responses of Glioblastoma Patient-Derived Cell Cultures to Drugs Reveals New Therapeutic Opportunities

“…A recent systematic review and meta-analysis confirmed a MGMT methylation status as a clinical biomarker in GBM patients, showing association with better overall and progression free survival in patients treated with alkylating agents [140]. Interestingly, the survival benefits were also observed in GBM patients irrespective of treatment [141]. A subgroup of patients treated with tyrosine kinase inhibitors (with or without alkylating agent in combination) showed a significant association of the MGMT methylation with overall survival.…”

Risk factors and prognostic implications of surgery-related strokes following resection of high-grade glioma

“…It is noteworthy, however, that our results may have been influenced by the fact that 12% of our study population were IDH-mutant WHO grade 4 astrocytoma patients, who tend to have longer survival. Interestingly, none of the stroke patients were IDH-mutant, which may have also contributed to the shorter survival in this group 25,26 . We do not have a clear explanation for this finding and further studies should validate whether IDH-mutant tumors indeed tend to have less intra-operative strokes.…”

High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma

“…These include MMP-2, MMP-9, VEGFA, and YKL40 [ 1 , 17 , 18 , 19 , 20 ]. The role of MMP-2 and MMP-9 in the degradation of ECM significantly contributes to tumor invasion and the aggressiveness of GBs [ 1 ], while the aberrant expression of VEGFA is suggested to drive angiogenesis and tumorigenesis [ 15 , 21 ]. YKL40 (also known as CHI3L1) has been described as having an important role in glioma cell proliferation [ 22 ].…”