Development and Validation of a Liquid-Liquid Phase Separation-Related Gene Signature as Prognostic Biomarker for Low-Grade Gliomas.

Aim: To explore whether the liquid-liquid phase separation- (LLPS-) related genes were potential prognostic markers that could contribute to the further classification of low-grade gliomas (LGGs). Methods: The LLPS-related genes were subjected to functional enrichment analysis. The univariable, least absolute shrinkage and selection operator, and multivariable stepwise Cox regression analyses were performed to develop an LLPS-related gene signature (GS) in the discovery data set. The biological characteristics of the high-risk LGG were explored using gene set enrichment analysis. Two independent external data sets were used to validate the LLPS-related GS. Results: LLPS-related genes are involved in multiple important cancer-related biological processes and pathways in LGG. Nine LLPS-related genes were identified to construct the LLPS-related GS, which was significantly associated with the prognosis of LGG patients. The LLPS-related GS could successfully divide patients with LGG into high- and low-risk groups, and the high-risk group showed a poorer prognosis than the low-risk group. Furthermore, the LLPS-related GS was independent of IDH and 1p19q status. Several cancer-related pathways may be more active in high-risk LGGs, such as IL6 JAK STAT3 signaling pathway. The LLPS-related GS was successfully validated with two independent external data sets. Conclusion: We developed and validated a novel LLPS-related GS for risk stratification of LGG. Our findings may provide more precise management for LGGs and a useful reference for LLPS mechanism to link LGG studies.

A meta-analysis of parental smoking and the risk of childhood brain tumors.

OBJECTIVE: Previous studies regarding the association between parental smoking and the risk of childhood brain tumors (CBT) have reported inconsistent results. We performed a meta-analysis to summarize evidence on this association and to quantify the potential dose-response relationship. METHODS: A systematic literature search was conducted in the Medline and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose-response meta-analysis was also performed for studies that reported categorical risk estimates for a series of smoking exposure levels. RESULTS: A total of 17 studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking before pregnancy, and paternal smoking before pregnancy were 0.96 (0.86-1.07), 1.09 (0.97-1.22), 0.93 (0.85-1.00), and 1.09 (1.00-1.20), respectively. Dose-response meta-analysis also showed no significant association between parental smoking and the risk of CBT. CONCLUSIONS: Findings from our meta-analysis indicate that parental smoking may not be associated with a risk of CBT.

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies.

Studies investigating the association between the intron 16 insertion/deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) gene and risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratios (OR) and 95% confidence limits (CLs) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 744 ICH cases and 1411 controls. The combined results based on all studies showed that ICH cases had a significantly lower frequency of ID genotype (OR (codominant model) = 0.43, 95% CL = 0.22, 0.84, p = 0.01). In the subgroup analysis by race, we found that ICH cases had a significantly lower frequency of II genotype in Asians (OR (recessive model) = 0.50, 95% CL = 0.38, 0.66, p < 0.001; OR (codominant model) = 0.25, 95% CL = 0.09, 0.71, p = 0.009). In conclusion, our meta-analysis suggests that ACE I/D polymorphisms are associated with ICH, especially in Asians.