CAGE基因mRNA水平表达与直肠癌关系的初步研究

A Preliminary Study on Relationship between the mRNA Expression of CAGE Gene and Rectal Cancer

目的:探讨直肠癌组织中癌相关基因(cancer-associated gene,CAGE)mRNA水平表达与直肠癌发生及临床分期、淋巴结转移的关系。方法:对我院2014年2月-2014年10月间肠镜室检查的标本,按病理检查结果分为3组:直肠癌组(80例;为直肠癌患者标本),大肠腺瘤组(38例;为大肠腺瘤患者标本),对照组(40例;为距肿瘤边缘10 cm以上标本)。采用RT-PCR法检测并比较各组CAGE在mRNA水平表达情况。甲基化特性PCR法(methylation-specific PCR,MSP)检测CAGE基因启动子的甲基化情况。将直肠癌患者分为CAGE基因甲基化患者组和CAGE基因去甲基化患者组,比较两组临床分期和淋巴结转移率。结果:与对照组相比,直肠癌组和大肠腺瘤组的CAGE mRNA水平表达明显升高(P<0.01);直肠癌组高于大肠腺瘤组(P<0.01)。3组间的基因启动子区的去甲基化阳性率差异有统计学意义(P<0.01)。在直肠癌组中,CAGE去甲基化阳性患者的淋巴结转移率为73.8%(48/65),CAGE去甲基化阴性患者的淋巴结转移率为33.3%(5/15),两者相比差异有统计学意义(P<0.01)。临床分期为I-Ⅱ期的CAGE基因启动子区的去甲基化直肠癌患者占24.6%(16/65),临床分期为Ⅲ-Ⅳ期的占75.4%(49/65);而甲基化的直肠癌患者中,临床分期为I-Ⅱ期的占66.7%(10/15),Ⅲ-Ⅳ期的占33.3%(5/15),两组间差异有统计学意义(P<0.01)。结论:直肠癌组织和大肠腺瘤组织中,CAGE mRNA水平呈高表达。直肠癌的CAGE基因mRNA水平表达高于正常粘膜组织和大肠癌腺瘤组织。CAGE基因启动子区的去甲基化与淋巴结转移及临床分期密切相关。

Objective： To investigate the relationship between the mRNA expression of cancer-associated gene（CAGE） and occurrence, clinical stage and lymph node metastasis of rectal cancer. Methods： The specimens from patients accepting endoscopic examination from February 2014 to October 2014 were divided into three groups according to pathological diagnosis, rectal cancer group（n=80, rectal cancer specimens）; colorectal adenoma group（n=38, rectal cancer specimens）; and control group（n=40, normal mucosal tissues 10 cm beyond rectal cancer）. The expression of CAGE in mRNA level was detected through RT-PCR and the methylation of CAGE promoter was tested through methylation-specific PCR. The rectal cancer patients were subdivided into two groups, the patients with CAGE promoter methylation and without CAGE promoter methylation. The clinical stage and lymph node metastasis was compared between the two groups. Results： RT-PCR showed higher expression CAGE in mRNA level in rectal cancer group and in colorectal adenoma group than control group（P〈0.01）; there was higher expression CAGE in mRNA level in rectal cancer group than that in colorectal adenoma group（P〈0.01）. The difference of positive rate of demethylated CAGE promoter between three groups was statistically significant（P〈0.01）. Out of the patients with positive demethylated CAGE promoter in rectal cancer group, 73.8 %（48/65） had lymphatic metastasis; whilst 33.3%（5/15） out of those with negative demethylated CAGE promoter（P〈0.01）. Out of the patients with positive demethylated CAGE promoter in rectal cancer group, 24.6%（16/65）were clinical stage I- Ⅱ and 75.4 %（49/65）were clinical stage Ⅲ-Ⅳ; whilst out of the patients with negative demethylated CAGE promoter in rectal cancer group, 66.7 %（10/15）were clinical stage I-Ⅱand 33.3 %（5/15）were clinical stage Ⅲ-Ⅳ. There were statistical difference between the two groups（P〈0.01）. Conclusions：CAGE mRNA was highly expressed in rectal cancer tissues and in colorectal adenoma tissues. Demethylated state of CAGE promoter is closely related with lymphatic metastasis and clinical stage.