F10 gene hypomethylation, a putative biomarker for glioma prognosis
F10 gene hypomethylation, a putative biomarker for glioma prognosis
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F10 基因低甲基化，胶质瘤预后的假定生物标志物
DOI：
10.1007/s11060-011-0775-2
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发表时间：
2012-05-01
影响因子：
3.9
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
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作者：
Liu, Xiaoping;Tang, Hailin;Li, Guiyuan
肿瘤通常以胞嘧啶甲基化的不平衡为特征，包括CpG岛的低甲基化。本研究采用亚硫酸氢盐测序PCR技术检测了96例胶质瘤患者肿瘤组织及胶质瘤细胞U251、SF 767和SF 126中凝血因子X（F10）基因启动子甲基化状态，并采用免疫组化方法评价了启动子低甲基化对蛋白表达的影响。研究表明，SF 126、SF 767和U251细胞中F10的去甲基化率分别为38.6%、26.4%和24.3%。在82.3%的胶质瘤组织中检测到F10低甲基化，而在正常脑组织中未检测到F10低甲基化，且F10低甲基化与其蛋白表达显著相关。F10低甲基化与性别、年龄、肿瘤分级无明显关系。F10低甲基化、蛋白表达和总生存期（OS）之间的相关性具有统计学意义。胶质瘤中F10启动子的低甲基化解释了F10编码蛋白FX的过表达和一部分患者的侵袭性生物学行为。此外，在F10低甲基化组中，F10过表达的患者的OS比无F10过表达的患者短。检测肿瘤中的这些表观遗传变化可以提供关于预后的重要信息。
Tumors are usually characterized by an imbalance in cytosine methylation, including hypomethylation of CpG islands. In this study, bisulfite sequencing PCR was used to assess the promoter methylation status of coagulation factor X (F10) gene in tumors of 96 glioma patients and in glioma cells U251, SF767, and SF126, and the effect of promoter hypomethylation on protein expression was evaluated immunohistochemically. The study showed that the demethylation ratio of F10 in SF126, SF767, and U251 cells was 38.6, 26.4, and 24.3% respectively. Hypomethylation of F10 was detected in 82.3% of glioma specimens and in no normal brain tissues, with significant correlation with its protein expression. However there was no remarkable relationship between F10 hypomethylation and sex, age, and advanced tumor grade. The correlation between F10 hypomethylation, protein expression, and overall survival (OS) was statistically significant. Hypomethylation of F10 promoter in gliomas accounted for F10 encoding protein FX overexpression and aggressive biological behavior in a subset of patients. Furthermore, in the F10 hypomethylation group, OS was shorter for patients with F10 overexpression than for those without. Detection of these epigenetic changes in tumors may provide important information regarding prognosis.