Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: association with tumor WHO grade and clinical outcome

Purpose The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics. Methods We evaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing. Results We demonstrated the direct statistical correlation between the level of methylation of all HOXA genes examined and WHO grading. Moreover, in glioblastoma patients, higher level of HOXA9 and HOXA10 methylation significantly correlated with increased survival probability (HOXA9-HR: 0.36, P = 0.007; HOXA10-HR: 0.46, P = 0.045; combined HOXA9 and 10-HR 0.28, P = 0.004). Conclusions This study identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma patients. Our data indicate that these epigenetic changes may be biomarkers of clinically different subgroups of glioma patients that could eventually benefit from personalized therapeutic strategies.