胰腺癌Kras基因突变与Glut1高表达协同促进肿瘤发生-东南大学学报医学版

胰腺癌Kras基因突变与Glut1高表达协同促进肿瘤发生

单位：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

分类号：R735.9

出版年·卷·期（页码）：2015·34·第六期（982-986）

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 in 26 (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.

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