为了改善胶质瘤患者的预后,早期诊断和治疗需要更好的工具。血清无细胞DNA甲基化水平的Alu,MGMT,通过亚硫酸氢盐测序检测了124例神经胶质瘤患者和58例健康对照的P16,RASSF1A。Alu的甲基化水平中位数为46.15%(IQR,36.57%-54.00%)和60.85%(IQR,神经胶质瘤患者和健康对照组分别为57.23%-65.68%)。胶质瘤样本中MGMT的甲基化水平中位数为64.65%(IQR,54.87%-74.37%),而38.30%(IQR,34.13%-45.45%)在健康对照组中,和所有显示显着差异,包括P16。然而,神经胶质瘤患者RASSF1A的中位甲基化水平无显著改变.此外,血清中Alu和MGMT的甲基化水平具有较好的诊断价值,高于P16。有趣的是,Alu和MGMT的组合确定了额外的患者,这两个诊断都遗漏了。在Alu组,与低水平患者相比,高水平患者的生存率更高,在MGMT组中观察到类似的结果。在本研究中,我们证明血清中Alu和MGMT的甲基化水平比P16具有更好的诊断价值。此外,Alu和MGMT联合分析对胶质瘤诊断的敏感性更高.因此,血清Alu和MGMT甲基化水平可能代表神经胶质瘤患者的新预后因素.
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.