Alu hypomethylation and MGMT hypermethylation in serum as biomarkers of glioma

Abstract

In order to improve prognosis of glioma patients, better tools are required for early diagnosis and treatment. Serum cell-free DNA methylation levels of Alu, MGMT, P16, RASSF1A from 124 glioma patients and 58 healthy controls were detected by the bisulfite sequencing. The median methylation level of Alu was 46.15% (IQR, 36.57%–54.00%) and 60.85% (IQR, 57.23%–65.68%) in glioma patients and healthy controls respectively. The median methylation level of MGMT in glioma samples was 64.65% (IQR, 54.87%–74.37%) compared to 38.30% (IQR, 34.13%–45.45%) in healthy controls, and all revealed significant differences including P16. However, the median methylation level of RASSF1A was not significantly altered in glioma patients. Furthermore, the methylation levels of Alu and MGMT in serum had a good diagnostic value, and was higher than P16. Interestingly, combination of Alu and MGMT identified additional patients, which were missed by either diagnosis alone. In the Alu group, the patients with high levels were associated with an increased survival rate compared to those who with low levels, with similar results observed in the MGMT group. In the present study, we demonstrated that the methylation level of Alu and MGMT in serum had a better diagnostic value than P16. Moreover, combined analysis of Alu and MGMT showed higher sensitivity for glioma diagnosis. Therefore, both serum Alu and MGMT methylation levels may represent a novel prognostic factor for glioma patients.