Association between H3K4 methylation and cancer prognosis: A meta-analysis

Abstract

Background: Histone H3 lysine 4 methylation (H3K4 methylation), including mono-methylation (H3K4me1), di-methylation (H3K4me2), or tri-methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta-analysis to examine the association between H3K4 methylation and cancer prognosis. Methods: A comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. Results: A total of 1474 patients in 10 studies were enrolled in this meta-analysis. The pooled HR of 1.52 (95% CI 1.02–2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27–0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival. Conclusion: This meta-analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings.