Zhang Feng, Liu Yifan, Zhang Zhiwen, Li Jie, Wan Yi, Zhang Liying, Wang Yangmei, Li Xia, Xu Yuqiao, Fu Xin, Zhang Xiumin, Zhang Ming, Zhang Zhekai, Zhang Jing, Yan Qingguo, Ye Jing, Wang Zhe, Chen Charlie Degui, Lin Wei, Li Qing
State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
State Key Laboratory of Molecular Biology, Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Sci Rep. 2016 Feb 11;6:20882. doi: 10.1038/srep20882.
Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that IDH1 mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA.
目前，世界卫生组织II级弥漫性星形细胞瘤（DA）可靠的预后生物标志物仍然有限。我们研究了5-羟甲基胞嘧啶（5hmC）水平与胶质瘤患者临床病理特征之间的关系，5hmC是由10-11易位（TET）酶催化5-甲基胞嘧啶（5mC）产生的氧化产物。我们使用一种已鉴定的抗5hmC抗体，对287例胶质瘤病例进行了免疫组织化学检测。我们发现，大多数胶质瘤中5hmC水平不同程度降低，且5hmC降低与胶质瘤患者的高病理分级和生存期缩短密切相关。在多变量分析中，5hmC在整个患者队列中没有独立的预后价值。然而，胶质瘤亚型内的多变量分析显示，5hmC仍然是局限于DA的预后标志物。此外，我们通过DNA测序检测到，IDH1突变与DA患者的良好生存期相关。最后，我们检测到5hmC/KI67组合是DA再分层的有用预后标志物。
