葡萄糖调节蛋白78在胃癌组织中的表达及其临床意义  

GRP78 expression in gastric cancer and its clinical significance

作　　者：杨磊[1] 杨书云[1] 季建美[1] 曹永峰[1] 季从飞[1] 季进锋[1] 徐薇薇[1] 王建红[1] 

机构地区：[1]南通大学附属肿瘤医院肿瘤内科,226361

出　　处：《中华肿瘤杂志》2013年第11期837-842,共6页Chinese Journal of Oncology

基　　金：基金项目：南通市科技局指令性课题（S2010014）

摘　　要：目的探讨葡萄糖调节蛋白78（GRP78）在胃癌组织中的表达及其临床意义。方法收集2006年1月至2010年5月237例胃癌患者的临床资料。采用免疫组化法检测GRP78在胃癌组织中表达的情况，采用三磷酸腺苷生物荧光法（ATP—TCA）检测胃癌常用化疗药物及化疗方案的敏感性，分析GRP78表达与胃癌患者临床病理特征、化疗药物敏感性和无病生存时间（DFS）的关系。结果GRP78在胃癌组织中的阳性表达率为68．8％（163／237）。GRP78表达与胃癌患者年龄和性别无关，与肿瘤浸润深度、组织学分级、TNM分期和淋巴结转移有关（均P〈0．05），且其高表达与胃癌细胞对化疗药物的耐药性有关。GRP78阴性和阳性患者的DFS分别为（53．6±0．9）个月和（38．3±0．8）个月，差异有统计学意义（P=0．041）。进一步的亚组分析显示，在术后采用含紫杉类药物化疗组中，GRP78阴性和GRP78阳性患者的DFS分别为（58．6±2．6）个月和（49．1±2．7）个月，但差异无统计学意义（P=0．111）。在术后采用不含紫杉类药物化疗组中，GRP78阴性和阳性患者的DFS分别为（45．5±1．9）个月和（35．1±2．2）个月，差异有统计学意义（P=0．038）。在GRP78阳性的胃癌患者中，含紫杉类药物化疗组和不含紫杉类药物化疗组患者的DFS分别为（49．1±2．7）个月和（35．1±2．2）个月，差异有统计学意义（P=0．017）。单因素分析显示，组织学分级、TNM分期、淋巴结转移、GRP78表达与胃癌患者DFS有父（均P〈0．05）。多因素分析显示，GRP78表达和TNM分期是影响胃癌患者DFS的独立因素（均P〈0．05）。结论GRP78可作为衡量胃癌恶性程度和化疗药物敏感性的分子标志物，检测GRP78的表达可能有助于指导胃癌患者的化疗及预后判断。Objective To investigate the clinical value of the expression of glucose regulated protein 78 （GRP78） for assessment of severity, chemoresistance and prognosis in patients with gastric adenocarcinoma （GC） . Methods A cohort of 237 patients with gastric cancer was included in this study. 160 patients of them were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78 expression was detected by immunohistochemistry and 80 patients of them were tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay （ATP-TCA）. In addition, the relationships were analyzed between GRP78 and age, gender, tumor differentiation, invasion, disease stage, lymph node metastasis and chemoresistance as well as disease-free survival （DFS）. Results The positive rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the initiation of chemotherapy. The positive GRP78 expression was significantly correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph node metastasis （ all P 〈 0.05 ）, not correlated with gender and age, and high GRP78 expression was associated with the chemoresistance of the gastric cancer cells to chemotherapeutic agents. Negative GRP78 expression was associated with higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group and GRP78-negative group was （53.6 ± 0.9 ） months and （ 38.3 ± 0.8 ） months, respectively （P = 0. 041 ）. Interestingly, subgroup analysis revealed that the DFS in GRP78-negative andpositive patients treated with taxane-containing chemotherapy was （58.6 ± 2.6） months and （49.1 ± 2.7）months, respectively, but the difference was statistically not significant （ P =0. 111 ）. In contrast, in the subset of GRP78-negative and-positive patients treated with taxane-containing regimens, the DFS was （45.5 ± 1.9） months and （35.1 ±2.2） months, respectively, showing a significant difference （P =0.038）. In the group of patients with positive GRP78 expression,

关 键 词：胃肿瘤 葡萄糖调节蛋白78 外科手术 药物疗法 抗药性 肿瘤 预后 

分 类 号：R735.2[医药卫生—肿瘤]