Detection of serum Alu element hypomethylation for the diagnosis and prognosis of glioma

Abstract

Global genomic hypomethylation is a hallmark of cancer in humans. In the present study, the feasibility of measuring hypomethylation of Alu elements (Alu) in serum and its clinical utility were investigated. Tumor tissues and matched serum specimens from 65 glioma patients and serum samples from 30 healthy controls were examined for Alu hypomethylation by bisulfite sequencing. The median serum Alu methylation level was 47.30 % in patients (interquartile range (IQR), 35.40-54.25 %) and 57.90 % in the controls (IQR, 55.25-61.45 %). The median Alu methylation level in tumor samples was 40.30 % (IQR, 36.80-54.20 %), which shows the correlation of Alu hypomethylation between tumor and serum samples (r = 0.882) in the study group. The methylation level was higher in the low-grade glioma group than in the high-grade group both in tumor and serum samples. A correlation between high methylation level and longer survival time was detected in tumor and serum samples. Receiver operating characteristic curve analysis showed that the area under the curve for diagnosis was 0.861 (95 % confidence interval, 0.789-0.933), suggesting that Alu hypomethylation in serum may be of diagnostic value. Our results indicate that the detection of Alu hypomethylation in serum may be clinically useful for the diagnosis and prognosis of glioma.