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Background  Lower-grade gliomas (LGGs) is characteristic with great difference in prognosis. Due to limited prognostic biomarkers, it is urgent to identify more molecular markers to provide a more objective and accurate tumor classification system for LGGs.    Methods  In the current study, we performed an integrated analysis of gene expression data and genome-wide methylation data to determine novel prognostic genes and methylation sites in LGGs.    Results  To determine genes that differentially expressed between 44 short-term survivors (<2 years) and 48 long-term survivors (≥2 years), we searched LGGs TCGA RNA-seq dataset and identified 106 differentially expressed genes.  SERPINA5  and  TIMP1  were selected for further study. Kaplan–Meier plots showed that  SERPINA5  and  TIMP1  expression were significantly correlated with overall survival (OS) and relapse-free survival (RFS) in TCGA LGGs patients. We next validated the correlation between the candidate genes expression and clinical outcome in CGGA LGGs patients. Multivariate analysis showed that  TIMP1  mRNA expression had a significant prognostic value independent of other variables (HR = 4.825, 95% CI = 1.370–17.000,  P  = 0.014). Then, differential methylation sites were identified from differentially candidate gene expression groups, and all four methylation sites were significantly negatively correlated with gene expression (spearman  r  <  − 0.5,  P  < 0.0001). Moreover, hyper-methylation of four methylation sites indicated better OS ( P  < 0.05), and three of them also shown statistical significantly association with better RFS, except for  SERPINA5  cg15509705 ( P  = 0.0762).    Conclusion  Taken together, these findings indicated that the gene expression and methylation of  SERPINA5  and  TIMP1  may serve as prognostic predictors in LGGs and may help to precise the current histology-based tumors classification system and to provide better stratification for future clinical trials.

Identification of gene expression and DNA methylation of SERPINA5 and TIMP1 as novel prognostic markers in lower-grade gliomas