Zhou Jianbo, Xiao Xuping, Yi Hongmei, Wang Jihua, Wang Xiaoan, Zhang Qiuhang
Department of Otolaryngology and Head-Neck Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China.
ORL J Otorhinolaryngol Relat Spec. 2012;74(3):164-71. doi: 10.1159/000338613. Epub 2012 May 31.
Gp96 (GRP94) is a chaperone that is responsible for molecular folding and assembly of proteins. To investigate correlations among Gp96 expression, sensitivity to radiotherapy and clinical features of nasopharyngeal carcinoma (NPC), the expression of Gp96 in 98 NPC samples was analyzed by immunohistochemistry and Western blotting at the protein level, and by real-time PCR at the mRNA level. Clinicopathological features, including stage, sex, grade and survival, were compared between the high and low Gp96 expression groups. As a result, Gp96 was expressed at a higher level in NPC tissues than in noncancerous nasopharyngeal mucosa (p = 0.001). Univariate analysis suggested that a higher Gp96 expression level was associated with significantly decreased disease-free and 5-year survival rates (p = 0.000, p = 0.000, respectively). Multivariate Cox proportional-hazard regression analysis, which adjusts for clinicopathological variables, indicated that it was only associated with the 5-year overall survival rate (p = 0.002). Furthermore, patients with high Gp96 expression levels were significantly more resistant to radiotherapy (p = 0.001). These data are the first indication of a positive correlation between Gp96 expression levels and radiosensitivity and 5-year survival rate. Gp96 might serve as a novel candidate marker for predicting the long-term prognostic outcome of NPC.
糖蛋白96（GRP94）是一种伴侣蛋白，负责蛋白质的分子折叠和组装。为了研究糖蛋白96表达、对放疗的敏感性与鼻咽癌（NPC）临床特征之间的相关性，采用免疫组织化学和蛋白质印迹法在蛋白质水平分析了98例NPC样本中糖蛋白96的表达情况，并通过实时定量聚合酶链反应在mRNA水平进行分析。比较了糖蛋白96高表达组和低表达组之间的临床病理特征，包括分期、性别、分级和生存率。结果显示，NPC组织中糖蛋白96的表达水平高于非癌性鼻咽黏膜（p = 0.001）。单因素分析表明，糖蛋白96表达水平较高与无病生存率和5年生存率显著降低相关（分别为p = 0.000，p = 0.000）。多因素Cox比例风险回归分析对临床病理变量进行了校正，结果表明其仅与5年总生存率相关（p = 0.002）。此外，糖蛋白96表达水平高的患者对放疗的耐受性明显更强（p = 0.001）。这些数据首次表明糖蛋白96表达水平与放射敏感性和5年生存率之间呈正相关。糖蛋白96可能作为预测NPC长期预后结果的新型候选标志物。
