肺鳞癌、肺腺癌Ki-ras和p53基因序列分析

SEQUENCE ANALYSE OF KI-RAS AND P53 GENE IN PATIENTS WITH LUNG SQUAMOUS CANCER AND LUNG ADENOCARCINOMA

目的 :研究肺鳞癌、腺癌与Ki-ras基因外显子 1,2及p5 3基因外显子 7,8突变谱并观察肺鳞癌、腺癌预后同Ki-ras和 p5 3基因突变的关系。方法 :用PCR和测序方法分析 33例肺鳞癌和 2 7例肺腺癌Ki-ras基因外显子 1,2和 p5 3基因外显子 7,8错义突变。并追踪观察突变者和非突变者的二年存活率。结果 :肺鳞癌中发现 5例 (15 .16 % )Ki-ras基因突变和 12例 (36 .37% )p5 3基因突变 ;肺腺癌中发现 2例 (7.4 1% )Ki-ras基因突变和 7例 (2 5 .93% ) p5 3基因突变 ,两型肺癌间Ki-ras和p5 3基因突变阳性率差异均无统计学意义 (P>0 .0 5 ) ;肺鳞癌、腺癌中 p5 3基因突变总阳性率为 31.6 7% ,Ki-ras基因突变总阳性率仅 11.6 7% ,p5 3基因突变率高于Ki-ras基因突变率 (P <0 .0 5 )。p5 3基因突变谱与一般报道相似。Ki-ras基因突变情况与一般报道有所不同 ,未发现一般文献报道较多的第 12位等密码子突变 ,发现有第 6位密码子纯合性突变和第 31位和第 79位密码子杂合性突变。预后追踪显示 :无突变的病例 2年生存率为 4 0 % ,存在突变的病例 2年生存率仅 12 %。结论 :肺鳞癌、腺癌的Ki-ras和 p5 3基因突变谱较广 ,肺鳞癌和腺癌的预后均与这两个基因突变有关。

Objective:To investigate mutational spectra of Ki-ras gene exons 1,2 and p53 gene exons 7,8 in patients with lung squamous cancer and lung adenocarcinoma and to look into prognosis of patients with Ki-ras or p53 mutation and with no mutation. Methods:60 patients with lung cancer in all were collected,group A included 33 cases of lung squamous cancer, group B included 27 cases of lung adenocarcinoma. Polymerase chain reaction (PCR) and DNA sequencing methods were used to analyse Ki-ras oncogene exons 1,2 and p53 suppressive gene exons7,8. Two years' survival rates were compared between patients who had a Ki-ras mutation or p53 mutation and those had no mutation.Results:The difference of positive mutation rate between group A,which were 5 cases (15.6%) ki-ras mutation and 12 cases(36.37%) p53 mutation, and group B,which were 2 cases (7.41%) ki-ras mutation and 7 cases (25.93%) p53 mutation,was no statistical significance ( P > 0.05). In all the 60 cases of lung cancer, total positive mutation rate of p53 gene (19/60) was obviously higher than that of Ki-ras (7/60)( P < 0.05). Our result of p53 point mutation was similar to former report. The sequence analyse of ki-ras gene showed no ki-ras gene codon 12 mutation in all the 60 patients,but codon 6,31 and 79 mutation were found. It also showed that only 3 out of 25(12%) patients who had a ki-ras or p53 mutation catched two years' survive, which much lower.than that of patiems(14/35=40%) with no mutation. Conclusion:There are wide ki-ras and p53 mutational spectra in lung squamous cancer and lung adenocarcinoma,and there is a relation between prognosis of lung cancer and lung and ki-ras or p53 mutation.