MDM2-p53信号通路在癌症发生发展中的作用

Jing-peng Hao, S. Dong, B. He, Mei Han, Menglong Li, Penghao Li, B. Zheng
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摘要

目的探讨MDM2-p53信号通路在结直肠癌发生发展中的作用机制及p53与临床病理参数的相关性,进一步分析p53对预后的影响。方法收集86例结直肠癌患者的结直肠癌组织及邻近正常组织。采用免疫组织化学、Western Blot和实时荧光定量聚合酶链反应(RT-PCR)检测p53和小鼠双分钟2(MDM2)在结直肠癌及癌旁正常组织中的表达。采用Kaplan-Meier生存曲线分析患者预后。结果结直肠癌组织中p53、MDM2蛋白表达及mRNA表达均显著高于癌旁非癌组织(均P<0.01)。p53与MDM2的表达呈正相关(r=0.785)。p53在结直肠癌组织中的表达与肿瘤分化程度、TNM分期、淋巴结转移及浸润深度有良好的相关性(均P<0.05)。生存分析显示,p53高表达组患者的平均总生存时间为(53.92±1.56)个月,显著低于p53低表达组患者的平均总生存时间(69.16±3.72)个月,差异有统计学意义(χ2=14.78, P<0.01)。结论结直肠癌的发生风险和预后与MDM2-p53信号通路密切相关。P53可作为结直肠癌预后和治疗的潜在靶点。关键词:结直肠癌;p53;鼠双分2分;临床病理的功能;信号通路;预后
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Role of MDM2-p53 signaling pathway in the development of colorectal cancer
Objective To investigate the mechanism of MDM2-p53 signaling pathway in the development of colorectal cancer and correlation between p53 with clinicopathological parameters, so as to further analyze the effect of p53 on prognosis. Methods The colorectal cancer tissues and the adjacent normal tissues from 86 cases of patients with colorectal cancer were collected. The expression of p53 and murine double minute 2(MDM2) in colorectal cancer and adjacent normal tissues were detected by immunohistochemistry, Western Blot and real-time fluorescence quantitative polymerase chain reaction (RT-PCR). The prognosis of the patients was analyzed by the Kaplan-Meier survival curves. Results The protein expression and the mRNA expression of p53 and MDM2 in colorectal cancer tissues were significantly higher than that in the adjacent non-cancerous tissues (all P<0.01). A positive correlation was observed between the expression of p53 and MDM2 (r=0.785). The expression of p53 in colorectal cancer tissues were correlated well with the degree of tumor differentiation, TNM stage, lymph node metastasis and infiltration depth (all P<0.05). Survival analysis demonstrated that the mean overall survival time in p53 high expression group was (53.92±1.56) months which was significantly lower than that in p53 low expression group of (69.16±3.72) months, and the difference was statistically significant (χ2=14.78, P<0.01). Conclusions The risk and prognosis of colorectal cancer are closely related to the MDM2-p53 signaling pathway. p53 can be used as a potential target for the prognosis and treatment of colorectal cancer. Key words: Colorectal cancer; p53; Murine double minute 2; Clinicopathological features; Signaling pathway; Prognosis
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