The analysis of deregulated expression and methylation of the PER2 genes in gliomas

Growing evidence shows that disruption of circadian rhythm may be a risk factor in the development of glioma. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored and differential expression of the circadian clock genes in glioma and non-tumor cells may provide a molecular basis for manifesting this mechanism. The aim of the following study is to analyze the PER2 expression involved in the pathogenesis of glioma. Using immunohistochemical staining, methylation specific polymerase chain reaction techniques, we examined the expression of the most important clock genes, PER2, in 92 gliomas. The association between tumor grade (high-grade/low-grade gliomas) and expression of the investigated proteins (negative/positive) was assessed using the Spearman, Chi-square test and two-sample t-test, included in the Statistical Package for the Social Science, version 13.0. Using Spearman Correlation to analyse correlation between the expression of PER 2 and PER2 promoter methylation. Our results reveal disturbances in the expression of the period 2 (PER2) genes in most (52.17%) of the glimoa cells in comparison with the nearby non-cancerous cells and the PER2 gene deregulation is most probably by methylation of the PER2 promoter. Since, the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER2 gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of glioma.