Prognostic significance of genetic biomarkers in isocitrate dehydrogenase-wild-type lower-grade glioma: the need to further stratify this tumor entity - a meta-analysis.

Abstract

The clinical outcomes of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (e.g. TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases, including PubMed, Scopus, Web of Science and Virtual Health Library, were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival were calculated using a random-effect model weighted by an inverse variance method. A total of 11 studies were finally selected from 2274 articles for meta-analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR, 1.96; 95% CI, 1.42-2.70), H3F3A mutation (HR, 3.21; 95% CI, 1.86-5.55) and EGFR amplification (HR, 1.67; 95% CI, 1.02-2.74). However, CDKN loss, ATRX mutation and coexisting gain of chromosome 7/loss of chromosome 10 showed no clinical significance in this glioma entity. Our study results demonstrated that IDH-wt LGGs are heterogeneous in clinical outcome and not all tumors have a poor prognosis. The presence of TERT promoter mutation, H3F3A mutation and EGFR amplification showed negative prognostic impacts in this tumor entity. These genetic events can be used to better stratify patient outcomes.