胰腺癌Kras基因突变与Glut1高表达协同促进肿瘤发生  

Synergy of tumorigenesis between high-Glut1 expression and Kras mutation in pancreatic cancer

作　　者：吴丹[1] 王彩莲[2] 李春妍[3] 郑士亚 

机构地区：[1]东南大学医学院附属江阴医院肿瘤科,江苏江阴214400 [2]东南大学附属中大医院肿瘤科,江苏南京210011 [3]南京医科大学,江苏南京210029

出　　处：《东南大学学报（医学版）》2015年第6期982-986,共5页Journal of Southeast University(Medical Science Edition)

摘　　要：目的:探讨胰腺癌组织中Kras基因点突变的表达以及葡萄糖转运蛋白-1(Glut1)表达在促进癌细胞恶性增生中的意义及作用,研究两者之间的相关性。方法:收集46例胰腺癌患者组织蜡块,应用免疫组织化学染色技术检测Glut1在胰腺癌中的表达,荧光定量PCR测序法检测胰腺癌标本中Kras基因点突变率。结果:46例胰腺癌中Glut1的阳性表达为40例(86.9%),正常癌旁组织中Glut1不表达,两者差异有统计学意义(P<0.01)。Glut1的表达与年龄、肿瘤大小、肿瘤部位相关(P<0.05),与性别、淋巴结转移、神经侵犯、病理分级、临床分期、病理类型无关。在46例胰腺癌患者中有26例存在Kras基因点突变(56.5%),其中24例12密码子突变(G34D 3例,G35D 21例);2例13密码子突变(G38D 1例,C39D 1例)。Kras基因点突变与肿瘤大小、神经侵犯相关(P<0.05),与年龄、性别、淋巴结转移、肿瘤部位、临床分期、病理类型、病理分级无关。胰腺癌中Glut1蛋白呈高表达时,Kras基因存在明显突变,有明显相关性(r=0.99,P<0.05)。结论:Glut1高表达与Kras基因异常表达可能协同促进了胰腺癌的恶性病变。Objective： To analyze the relationship between overexpression of Glut1 and Kras mutations in pancreatic cancer. Methods： In 46 cases of pancreatic carcinoma and 46 cases of tumor adjacent normal pancreatic tissues,immunohistochemistry was performed for Glut1 expression status. Kras mutation status was also evaluated using PCR-based assays. Results： Glut1 expression was increased in 40（ 86. 9%） pancreatic cancer cases. At the same time,it was not expressed in adjacent controls（ P〈 0. 001）. The Glut1 overexpression was significantly associated with age（ 〈56,62. 5% vs 〉56,92. 1%,P〈0. 05）,tumor size（ 〈6 cm,92. 1% vs 〉6 cm,62. 5%,P〈0. 05）,tumor location（ head,100% vs non-head,71. 4%,P 〈0. 01）,Kras mutation was found in26（ 56. 5%） pancreatic cancer cases. The Kras mutation was associated with tumor size（ 〈6 cm,63. 2% vs 〉6 cm,25%, P〈0. 05）, nerve invasion（ absent,51. 3% vs present,88. 9%, P〈0. 05）. The Glut1 overexpression status was significantly correlated with Kras mutation status（ r = 0. 99,P〈0. 05）. Conclusion： Our results strongly suggest that overexpression of Glut1 is significantly correlated with Kras mutations in pancreatic cancer to increase the tumor genesis.

关 键 词：胰腺癌 KRAS基因 葡萄糖转运蛋白-1 糖酵解 

分 类 号：R735.9[医药卫生—肿瘤]