GRP78在胆管癌组织中的表达及其与预后的关系  

Expression of GRP78 in cholangiocarcinoma tissues and its relationship with prognosis

作　　者：高龙 马海东 白明圳 付文康 米宁宁 林延延[1,2] 岳平[1,2] 张金铎[1,2] 孟文勃 GAO Long;MA Haidong;BAI Mingzhen;FU Wenkang;MI Ningning;LIN Yanyan;YUE Ping;ZHANG Jinduo;MENG Wenbo(The First Clinical Medical College of Lanzhou University,Gansu Lanzhou 730000,China;Department of General Surgery,FirstHospital of Lanzhou University,Gansu Lanzhou 730000,China;The Key Laboratory of Biological Therapy and RegenerativeMedicine,Gansu Province,Gansu Lanzhou 730000,China)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000 [2]兰州大学第一医院普外科,甘肃兰州730000 [3]甘肃省生物治疗与再生医学重点实验室,甘肃兰州730000

出　　处：《现代肿瘤医学》2023年第15期2861-2867,共7页Journal of Modern Oncology

基　　金：国家自然科学基金面上项目(编号:81872036);甘肃省兰州市城关区科技计划项目(编号:2019RCCX0038,2019JSCX0092)。

摘　　要：目的:探讨葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)在胆管癌组织中的表达水平及其预后价值。方法:收集胆管癌组织标本,利用iTRAQ技术筛选胆管癌组织差异蛋白。采用qRT-PCR和Western blot方法检测GRP78的表达情况。利用组织芯片和免疫组化技术研究GRP78和胆管癌预后之间的相关性。结果:利用iTRAQ技术共筛选出147个差异蛋白,其中热休克蛋白70家族成员HSPA5(GRP78)在癌组织中异常高表达。Western blot发现癌组织中GRP78蛋白表达水平均高于癌旁组织,而且GRP78 mRNA平均相对表达量在癌组织和癌旁组织中分别是2.90和0.89,两者相差3.26倍,t=4.834,P<0.001。Kaplan-Meier曲线示GRP78高表达患者的中位总生存时间和无病生存时间分别为6.83和3.74个月,而GRP78低表达患者分别为12.01和11.70个月,GRP78高表达患者总生存率低且易复发,P<0.05。单因素Cox分析指出GRP78高表达、肿瘤直径≥5 cm、肝内胆管癌、血管侵犯阳性以及高TNM分期等与胆管癌患者总生存时间和无病生存时间密切相关(P均<0.05)。多因素Cox分析发现GRP78高表达和肝内胆管癌以及肿瘤直径≥5 cm皆是胆管癌患者复发的独立危险因素(P均<0.05),并且GRP78高表达是总生存时间的独立危险因素(P<0.05)。结论:GRP78在胆管癌组织中异常高表达,并且和胆管癌预后密切相关,是一个潜在的胆管癌预后指标和治疗靶标。Objective:To investigate the expression of GRP78 in cholangiocarcinoma and its prognostic value.Methods:The cancer tissues of patients with cholangiocarcinoma were collected,and differential proteomics was performed using iTRAQ.The expression of GRP78 was detected by qRT-PCR and Western blot.Tissue microarray and immunohistochemistry were used to study the correlation between GRP78 and prognosis.Results:A total of 147 differential proteins were screened by iTRAQ,among which heat shock protein 70 family member HSPA5(GRP78)was aberrantly highly expressed.The results of Western blot showed that GRP78 protein in cancer tissues was significantly higher than that in adjacent tissues,and the average relative expression of GRP78 mRNA was 2.90 and 0.89 in cancer tissues and adjacent tissues respectively,the difference between them was 3.26 times,t=4.834,P<0.001.Kaplan-Meier survival curves showed that the median overall survival time and disease-free survival time of patients with high GRP78 were 6.83 and 3.74 months respectively,while in patients with low GRP78 were 12.01 and 11.70 months respectively.Patients with high expression of GRP78 had a lower overall survival rate and were prone to relapse,P<0.05.Univariate Cox analysis indicated that high expression of GRP78,tumor volume≥5 cm,intrahepatic cholangiocarcinoma,positive vascular invasion and high TNM stage were closely related to the survival time and disease-free survival time(all P<0.05).Multivariate Cox analysis found that high expression of GRP78,intrahepatic cholangiocarcinoma and tumor volume≥5 cm were independent risk factors for recurrence(all P<0.05),and high expression of GRP78 was an independent risk factor for overall survival(P<0.05).Conclusion:GRP78 is highly expressed in cholangiocarcinoma.The high expression of GRP78 is closely related to poor prognosis and it is a potential prognostic marker and therapeutic target for cholangiocarcinoma.

关 键 词：胆道肿瘤 GRP78 胆管癌 预后 肿瘤标志物 

分 类 号：R735.8[医药卫生—肿瘤]