GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy.
GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy.
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DOI：
10.1186/1748-717x-6-136
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发表时间：
2011-10-12
期刊：
影响因子：
--
通讯作者：
Chang JT
中科院分区：
文献类型：
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作者：
Lin CY;Lin TY;Wang HM;Huang SF;Fan KH;Liao CT;Chen IH;Lee LY;Li YL;Chen YJ;Cheng AJ;Chang JT
口腔癌（ORC）是最常见的癌症，标准治疗是根治性手术和术后放疗。然而，局部失败仍然是一个主要问题，表明辐射抗性是一个重要的问题。我们以前的工作表明，GP96有助于鼻咽癌和口腔癌细胞系的放射抗性。在这项研究中，我们通过评估GP96表达及其与接受放射治疗的患者的疾病预后的关系来确定GP96在ORC中的临床意义。共纳入了79例在1999年10月至2004年12月期间接受根治性手术和术后放射治疗的ORC患者（77例男性，中位年龄：48岁）。病理分期Ⅱ、Ⅲ、Ⅳ期分别为16.5%、16.5%和67%。对于每个患者，获得一对癌组织和大体上相邻的正常粘膜。通过蛋白质印迹分析检测GP96表达，并确定其与临床病理状态的相关性。3年局部控制率（LRC）、无远处转移生存率（DMFS）、疾病特异性生存率（DSS）和总生存率（OS）分别为69%、79%、63%和57%。我们发现55名患者（70%）在肿瘤组织中显示出GP96过表达，这与较高的pN分期（p = 0.020）和肿瘤深度（> 10 mm）（p = 0.045）相关。淋巴结囊外扩散（ECS）和GP 96过表达预测不良LRC（p = 0.049和p = 0.008）。当按淋巴结ECS分层时，GP96的不良影响在3年LRC中仍然显著（p = 0.004）。在多变量分析中，GP96过表达也是LRC、DSS和OS的独立预测因子（p = 0.018，p = 0.011和p = 0.012）。GP96可能在口腔癌放射抵抗中发挥作用，而放射抵抗是口腔癌患者接受放射治疗时肿瘤侵袭性的原因。GP96可作为一种新的放射治疗预后指标。然而，需要进一步的独立研究来验证我们在更大范围内的发现。
Oral cavity cancers (ORC) are the most common cancers, and standard treatment is radical surgery with postoperative radiotherapy. However, locoregional failure remains a major problem, indicating radioresistance an important issue. Our previous work has shown that GP96 contributed to radioresistance in nasopharyngeal and oral cancer cell lines. In this study, we determined clinical significance of GP96 in ORC by evaluation of GP96 expression and its association with disease prognosis in patients receiving radiotherapy Total of 79 ORC patients (77 males, median age: 48 years old) receiving radical surgery and postoperative radiotherapy between Oct 1999 and Dec 2004 were enrolled. Patients in pathological stages II, III and IV were 16.5%, 16.5% and 67%, respectively. For each patient, a pair of carcinoma tissue and grossly adjacent normal mucosa was obtained. GP96-expression was examined by western blot analysis, and the association with clinicopathological status was determined. Three-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) rates were 69%, 79%, 63% and 57%, respectively. We found that 55 patients (70%) displayed GP96-overexpression in the tumor tissue, which correlated with a higher pN stage (p = 0.020) and tumor depth (> 10 mm) (p = 0.045). Nodal extracapsular spreading (ECS) and GP96-overexpression predicted adverse LRC (p = 0.049 and p = 0.008). When stratified by nodal ECS, the adverse impact of GP96 remained significant in three-year LRC (p = 0.004). In multivariate analysis, GP96-overexpression was also an independent predictor of LRC, DSS and OS (p = 0.018, p = 0.011 and p = 0.012). GP96 may play roles in radioresistance which attributes to tumor invasiveness in oral cancer patients receiving radiotherapy. GP96 may serve as a novel prognostic marker of radiotherapy. However, further independent studies are required to validate our findings in a larger series.