邱勇　周军格　陈俊瑜

【摘要】目的 探讨人巨细胞病毒IE1蛋白（HCMV-IE1）及WD重复蛋白5（WDR5）在高级别胶质瘤中的表达及意义。方法 采用免疫组织化学（免疫组化）方法检测HCMV-IE1和WDR5在60份高级别胶质瘤组织及20份正常脑组织中的表达，分析HCMV感染与WDR5的相關性及两者对胶质瘤预后的影响。结果 53 份（88.3%）高级别胶质瘤组织中的HCMV-IE1呈阳性表达，20份正常脑组织中均无HCMV-IE1表达（P < 0.001）;HCMV-IE1表达程度低者总生存率优于表达程度高者（P = 0.037）。49份（81.6%）高级别胶质瘤组织中WDR5表达阳性，11份（5.5%）正常脑组织中WDR5表达阳性（P = 0.009）。在60份高级别胶质瘤组织中，HCMV-IE1与WDR5同时高表达有27例（45.0%），同时低表达有14例（23.3%），HCMV-IE1表达与WDR5表达呈正相关（r = 0.336，P = 0.009）。结论 HCMV-IE1与高级别胶质瘤发生发展相关，是判断高级别胶质瘤预后的指标，其机制可能与HCMV-IE1和WDR5呈正相关有关联。

【关键词】人巨细胞病毒;高级别胶质瘤;WD重复蛋白5

【Abstract】Objective To investigate the expression and significance of human cytomegalovirus （HCMV）-IE1 protein and WDR5 protein in high grade glioma （HGG）.  Methods The expression of HCMV IE1 and WD repeat-containing protein （WDR5） proteins was detected by immunohistochemistry in 60 HGG tissues and 20 normal brain tissues. The correlation between HCMV infection and WDR5 protein and their influence on glioma prognoses were analyzed.  Results HCMV-IE1 protein was positively expressed in 53 HGG tissues （88.3%） while not expressed in 20 normal brain tissues （P < 0.001）. The overall survival rate of HGG patients with low expression level of HCMV-IE1 was better than those with high expression level of HCMV-IE1 （P = 0.037）. WDR5 protein expression was positive in 49 （81.6%） HGG tissues and in 11 （5.5%） normal brain tissues （P = 0.009）. Among 60 HGG tissues， 27 cases （45.0%） had simultaneously high expression HCMV-IE1 protein and WDR5 protein， and 14 cases （23.3%） had simultaneously low expression. The expression of HCMV-IE1 protein was positively correlated with that of WDR5 protein （r = 0.336， P = 0.009）. Conclusions HCMV-IE1 protein is associated with the initiation and development of HGG and is an indicator of the prognosis of HGG.The mechanism may be associated with the positive correlation between HCMV-IE1 and WDR5.

【Key words】Human cytomegalovirus;High grade glioma;WD repeat-containing protein

胶质瘤是最常见的原发性神经上皮细胞恶性肿瘤，WHO依据肿瘤的恶性程度将胶质瘤分为Ⅰ ～ Ⅳ级，其中低级别胶质瘤（LGG）包含Ⅰ、Ⅱ级，高级别胶质瘤（HGG）包含Ⅲ、Ⅳ级[1]。近年来随着神经外科显微手术技术及手术器械的发展，胶质瘤的手术治疗效果取得改善，但胶质瘤患者的预后未能获得根本的改善，尤其是HGG，肿瘤细胞呈侵袭性生长，术后肿瘤短期内就复发。手术辅以同步放射治疗或化学治疗的标准化方案是目前脑胶质瘤的主要治疗手段，由于HGG本身发生发展的分子机制，其容易对放射治疗及化学治疗发生抵抗，虽然各种新治疗方法不断涌现，但治疗效果仍较差[2]。目前肿瘤的靶向及免疫治疗等个体化精准治疗成为新的热点，而我们对于神经胶质瘤的病因学及遗传表征知之甚少。目前认为胶质瘤是一种“冷肿瘤”，肿瘤突变负荷较低，对传统放射治疗、化学治疗以及免疫治疗等方法响应有限，因而迫切需要研究胶质瘤可利用的新的靶点和遗传学表征，为胶质瘤的治疗提供新的思路。……