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目的 :了解 p5 3基因及其蛋白在大肠癌发生、转移过程中的动态变化以及p5 3变异与生存期的关系。方法 :以DenaturingGradientGelElectrophoresis (DGGE)及自动DNA序列分析检测p5 3基因exon 5~ 9。 结果 :41例被检病人中 2 6例呈p5 3变异 (6 3% ) ,其中 6例仅在肝转移灶发现 p5 3变异 ,其余均为原发灶、转移灶一致性的变异。另有 3例原发灶已有 p5 3变异的病人 ,在转移灶出现了新增加的变异。生存分析显示 ,在肝转移灶含变异型 p5 3的病人比含野生型 p5 3者具有更长的术后生存期。 结论 :大肠癌肝转移 ,p5 3变异主要开始于肠癌原发灶 ,并保持于转移至肝脏的癌细胞内 ,小部分p5 3变异也可以始发于转移灶。实施肝部分切除术的患者 ,转移癌灶含变异型 p5 3者的术后生存期比含野生型p5 3者长。
Objective : To understand the dynamic changes of p53 gene and its protein in the process of colorectal carcinogenesis and metastasis and the relationship between p53 mutation and survival time. METHODS: The p5 3 gene exon 5-9 was detected by DenaturingGradientGelElectrophoresis (DGGE) and automated DNA sequence analysis. RESULTS: Of the 41 patients, 26 cases were found to have p53 mutation (63%), of which 6 cases were found to have p53 mutations only in liver metastases. The rest were all consistent with primary lesions and metastatic lesions. In addition, 3 cases of p53 mutations were found in the primary tumors, and new mutations appeared in the metastases. Survival analysis showed that patients with variant p53 in liver metastases had a longer postoperative survival than those with wild type p53. Conclusion : In colorectal liver metastases, p53 mutations mainly originate from the primary tumors of the intestine and remain in the cancer cells that have metastasized to the liver. A small number of p53 mutations can also originate in metastases. In patients undergoing partial hepatectomy, metastatic p53 patients had a longer postoperative survival than those with wild type p53.