GREM1在人胆管癌中的表达及临床意义  

Expression and clinical significance of GREM1 gene in human cholangiocarcinoma

作　　者：吕秀芳[1] 周晓倩[2] LV Xiufang;ZHOU Xiaoqian(Department of Pathology in Medical College,Nantong University,Jiangsu 226001;Department of Gastroenterology,Guiyang First People’s Hospital)

机构地区：[1]南通大学医学院病理学系,江苏226001 [2]贵阳市第一人民医院消化内科

出　　处：《交通医学》2020年第6期573-577,共5页Medical Journal of Communications

基　　金：国家自然科学基金资助项目(81502100);贵阳市临床重点学科支持项目(筑20180001)。

摘　　要：目的:研究GREM1在人胆管癌(CCA)中的表达,探讨其在临床诊疗中潜在的应用价值。方法:利用公共数据库分析GREM1基因在人体组织器官中表达的差异,应用qRT-PCR和免疫组化染色法检测胆汁淤积性肝硬化大鼠肝组织中GREM1基因和蛋白表达情况。检测84例胆管癌患者手术切除的癌组织及配对癌旁组织中GREM1蛋白表达,并分析其表达水平与患者临床病理特征及预后的关系。结果:GREM1基因在人体胆囊组织中高表达。与假手术组大鼠相比,胆汁淤积性肝纤维化大鼠肝组织中GREM1基因和蛋白表达水平显著增加,差异均具有统计学意义(P<0.0001)。与健康对照者相比,胆管癌组织中GREM1基因表达显著增加,差异有统计学意义(P<0.0001)。与配对癌旁组织相比,胆管癌组织中GREM1蛋白水平显著增加,差异有统计学意义(P<0.0001)。GREM1高表达与胆管癌细胞分化、AJCC分级、淋巴结转移和TNM分期均密切相关(P<0.05),与GREM1低表达组相比高表达组患者总体生存率和无病生存率显著缩短,差异均具有统计学意义(P<0.05)。结论:GREM1在人胆管癌中高表达,与患者预后不良相关,有望成为胆管癌防治的潜在靶点,也可以作为判断患者预后的指标。Objective:To study the expression of GREM1 gene in cholangiocarcinoma(CCA)and to explore its potential application value in clinical diagnosis and treatment.Methods:Public databases were used to analyze the tissue-specific expression of GREM1 in humans,and the differential expression of GREM1 in CCA patients and in healthy controls was compared.qRT-PCR and immunohistochemical staining were used to detect the expression of GREM1 mRNA and protein.Expression of GREM1 in CCA tissues was compared with that in the paired noncancerous tissues.The relationship between GREM1 protein level and the clinical pathological characteristics,and the prognosis of the patients was analyzed.Results:GREM1 gene was specifically expressed in human gallbladder tissue.GREM1 gene mRNA and protein expression were significantly increased in the liver tissue of cholestatic cirrhosis rats(P<0.0001),GREM1 protein was seen depositing in the extracellular matrix.Compared with the healthy controls,GREM1 cDNA level was significantly increased in CCA tissue(P<0.0001);compared with the paired noncancerous tissues,the protein level of GEM1 was significantly increased in cancer tissue(P<0.0001).The higher level of GREM1 protein was related to cell differentiation,AJCC grade,lymph node metastasis,and TNM stages(P<0.05).Compared with the low expression of GREM1,the overall survival and disease-free survival were significantly reduced(P<0.05).Conclusion:GREM1 gene is increased in human CCA and is associated with a poor prognosis,which suggests that this gene is expected to become a target for individualized treatment for CCA.

关 键 词：GREM1 胆管癌 胆管结扎 细胞外基质 

分 类 号：R735.8[医药卫生—肿瘤]