Yang Lei, Yang Shu-yun, Ji Jian-mei, Cao Yong-feng, Ji Cong-fei, Ji Jin-feng, Xu Wei-wei, Wang Jian-hong
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China.
Department of Medical Oncology, Nantong University Tumor Hospital, Nantong 226361, China. Email:
Zhonghua Zhong Liu Za Zhi. 2013 Nov;35(11):837-42.
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) .
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).
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 and-positive 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, the patients treated with taxane-containing chemotherapy had a longer DFS [(49.1 ± 2.7) months] than those without that treatment [(35.1 ± 2.2) months], showing a significant difference (P = 0.017). Univariate analysis revealed that DFS was correlated with histological grade, GRP78 expression and lymph node metastasis (all P < 0.05). Multivariate analysis showed that GRP78 expression and TNM staging were independent influencing factors for gastric cancer (both P < 0.05).
The results of our study suggest that GRP78 may be a novel biomarker for assessment of malignant degree and prediction of chemoresistance in gastric cancer, and may be helpful to chemotherapy planning and prognosis prediction in patients with gastric cancer.
探讨葡萄糖调节蛋白78（GRP78）表达在评估胃腺癌（GC）患者严重程度、化疗耐药性及预后中的临床价值。
本研究纳入237例胃癌患者。其中160例患者接受D2根治性胃切除术及辅助化疗。采用免疫组织化学法检测GRP78表达，其中80例患者通过ATP肿瘤化疗敏感性检测（ATP-TCA）进行体外癌症化疗敏感性测试。此外，分析GRP78与年龄、性别、肿瘤分化、浸润、疾病分期、淋巴结转移、化疗耐药性以及无病生存期（DFS）之间的关系。
化疗开始前，胃腺癌中GRP78表达的阳性率为68.8%。GRP78阳性表达与肿瘤浸润深度、低分化、TNM分期及淋巴结转移显著相关（均P<0.05），与性别和年龄无关，且GRP78高表达与胃癌细胞对化疗药物的耐药性相关。GRP78阴性表达与对两种药物及方案的更高敏感性相关。GRP78阳性组和阴性组的DFS分别为（53.6±0.9）个月和（38.3±0.8）个月（P=0.041）。有趣的是，亚组分析显示，接受含紫杉烷化疗的GRP78阴性和阳性患者的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）。相反，在接受含紫杉烷方案治疗的GRP78阴性和阳性患者亚组中，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表达阳性的患者组中，接受含紫杉烷化疗的患者DFS[（49.1±2.7）个月]长于未接受该治疗的患者[（35.1±2.2）个月]，差异有统计学意义（P=0.017）。单因素分析显示，DFS与组织学分级、GRP78表达及淋巴结转移相关（均P<0.05）。多因素分析表明，GRP78表达和TNM分期是胃癌的独立影响因素（均P<0.05）。
我们的研究结果表明，GRP78可能是评估胃癌恶性程度和预测化疗耐药性的新型生物标志物，可能有助于胃癌患者的化疗方案制定和预后预测。
