结直肠癌中MAD2和抑癌基因的表达及意义

Expression of MAD2 and tumor suppressor gene in the colorectal cancer and clinical significance

背景与目的:有丝分裂阻滞缺陷蛋白2(mitotic arrest deficient protein2,MAD2)是一种有丝分裂检查点成分,其与肿瘤的发生密切相关。本研究旨在了解结直肠癌中MAD2和抑癌基因表达概况,探寻在结直肠癌、腺瘤及正常结直肠黏膜组织中的表达差异,初步分析其临床意义。方法:通过实时荧光定量PCR(real-time fluorogentic quantitative polymerase chain reaction,RFQ-PCR)和免疫组织化学方法检测结直肠癌、腺瘤及正常结直肠黏膜组织中MAD2表达,并对结直肠癌组织中MAD2扩增产物进行测序。同时利用免疫组织化学方法检测结直肠癌中p53、p27、p21和p16蛋白的表达。结果:结直肠癌组织中MAD2的阳性表达明显高于腺瘤和正常结直肠黏膜组织(66.7%vs39.6%vs22.9%),三者比较差异有统计学意义(P<0.001)。MAD2表达与肿瘤分化和无瘤生存时间有关(P<0.05)。结直肠癌组织中未见MAD2基因突变。MAD2阳性表达与p53、p27、p21和p16阳性表达之间有统计学意义(P<0.05)。结论:基因MAD2和抑癌基因表达异常与结直肠癌产的发生发展有关,MAD2可能是结直肠癌预后的一种重要预测指标。

Background and purpose： MAD2 is one of the mitotic checkpoints and it is closely associated with tumors. Our aim was to study the expression of gene MAD2 and tumor suppressor gene in colorectal cancer and to demonstrate the relationship between the expression of gene MAD2 and tumor suppressor gene in colorectal cancer, adenoma and normal tissue and to evaluate their clinical significance. Methods： Immunohistochemistry method and real-time fluorescence quantitative PCR were used to analyze the expression of gene MAD2 in colorectal cancer, adenoma and normal tissue. PCR amplification and DNA sequencing were performed to detect the mutations of gene MAD2. p53, p27, p21 and p16 were determined in colorectal cancer and normal tissue by immunohistochemistry methods. Results： The expression of MAD2 in colorectal cancer was obviously higher than in adenoma and normal tissue （66.7% vs 39.6% vs 22.9%）, there were significant differences among colorectal cancers, adenoma and normal tissue （P〈0.001）, and it was also related to tumor differentiation and survival time （P〈0.05）. No mutation of gene MAD2 was found in colorectal cancer. There was a high relationship between positive expression of MAD2, p53, p27, p21 and p16 （P〈0.05）. Conclusion： Our data indicated that positive expressions of MAD2 and tumor suppressor gene were involved mainly in colorectal carcinogenesis and MAD2 was strongly associated with the prognosis of colorectal cancer.