Gong Mingjie, Shi Wei, Qi Jing, Shao Guoping, Shi Zhenghua, Wang Junxiang, Chen Jian, Chu Rongtao
Department of Neurosurgery, Changshu No. 2 People's Hospital (The 5th Clinical Medical College of Yangzhou University), Changshu, Jiangsu Province, China.
Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
Oncotarget. 2017 Aug 7;8(44):76797-76806. doi: 10.18632/oncotarget.20012. eCollection 2017 Sep 29.
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.
为了改善胶质瘤患者的预后，需要更好的工具用于早期诊断和治疗。采用亚硫酸氢盐测序法检测了124例胶质瘤患者和58例健康对照者血清中Alu、MGMT、P16、RASSF1A的游离DNA甲基化水平。胶质瘤患者和健康对照者中Alu的甲基化水平中位数分别为46.15%（四分位间距，36.57%-54.00%）和60.85%（四分位间距，57.23%-65.68%）。胶质瘤样本中MGMT的甲基化水平中位数为64.65%（四分位间距，54.87%-74.37%），而健康对照者为38.30%（四分位间距，34.13%-45.45%），包括P16在内所有结果均显示出显著差异。然而，胶质瘤患者中RASSF1A的甲基化水平中位数无明显改变。此外，血清中Alu和MGMT的甲基化水平具有良好的诊断价值，且高于P16。有趣的是，Alu和MGMT联合检测能识别出单独诊断时遗漏的额外患者。在Alu组中，高水平患者与低水平患者相比生存率增加，MGMT组也观察到类似结果。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具有更高的敏感性。因此，血清Alu和MGMT甲基化水平均可能代表胶质瘤患者的一种新的预后因素。
