肺腺癌组织EGFR突变与p53和COX-2表达相关性及其临床意义

发布时间：2018-12-25 18:23

【摘要】：目的针对表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗已成为肺癌精准治疗的典范,但多数患者在EGFR-TKI治疗有效后的8~16个月不可避免会出现获得性耐药。本研究探讨p53和COX-2在EGFR突变型晚期肺腺癌组织中的表达及其与患者临床特征的关系,并观察其表达对EGFR-TKI疗效的影响。方法选取2014-03-01-2016-01-31于郑州大学第二附属医院病理确诊为EGFR突变型晚期肺腺癌并接受EGFR-TKI治疗的43例患者,利用免疫组织化学法检测p53和COX-2在EGFR突变型晚期肺腺癌组织中的表达;χ~2检验分析其与临床特征之间的相关性;生存分析采用Kaplan-Meier法;并进一步对影响患者无进展生存期(progression-free survival,PFS)的因素采用Cox比例风险回归模型分析。结果 43例EGFR突变型晚期肺腺癌患者中,p53、COX-2表达阳性率分别为41.8%和53.4%。p53表达随年龄增长(χ~2=3.939,P=0.047)及肿瘤分化程度减低(χ~2=4.182,P=0.041)而升高。COX-2表达与年龄、性别、吸烟史、肿瘤分化程度、临床分期及EGFR基因突变类型均未见明显相关性(P0.05)。p53与COX-2表达无明显相关性,P0.05。患者接受EGFR-TKI治疗后,p53阴性组和阳性组中位PFS分别为12.0和7.5个月,差异有统计学意义,χ~2=4.726,P=0.030;COX-2阴性组和阳性组中位PFS分别为12.0和10.0个月,差异有统计学意义,χ~2=5.578,P=0.018。进一步行多因素Cox比例风险回归模型分析显示,p53(HR=0.450,P=0.046)和COX-2(HR=0.424,P=0.021)表达均为EGFR突变型晚期肺腺癌患者PFS的独立影响因素。结论 EGFR突变型晚期肺腺癌组织中,p53和COX-2表达可能促进肿瘤进展,有望成为EGFR-TKI疗效的预测因子。
[Abstract]:Objective (tyrosine kinase inhibitor,TKI, a tyrosine kinase inhibitor for epidermal growth factor receptor (epidermal growth factor receptor,EGFR) sensitive mutation, has become a model for accurate treatment of lung cancer. But most patients will inevitably develop acquired drug resistance 8 ~ 16 months after EGFR-TKI treatment. The aim of this study was to investigate the expression of p53 and COX-2 in EGFR mutant advanced lung adenocarcinoma and their relationship with clinical features and to observe the effect of p53 and COX-2 expression on the efficacy of EGFR-TKI. Methods Forty-three patients with advanced lung adenocarcinoma diagnosed pathologically in the second affiliated Hospital of Zhengzhou University and treated with EGFR-TKI were selected from 2014-03-01-2016-01-31. The expression of p53 and COX-2 in EGFR mutant late stage lung adenocarcinoma was detected by immunohistochemical method. 蠂 ~ 2 test was used to analyze the correlation with clinical features, Kaplan-Meier method was used to analyze survival, and Cox proportional risk regression model was used to analyze the factors affecting progressive survival (progression-free survival,PFS). Results in 43 patients with advanced lung adenocarcinoma with EGFR mutation, the positive rate of p53 and COX-2 was 41.8%, the expression of 53.4%.p53 increased with age (蠂 ~ 2 + 3.939) and the degree of tumor differentiation decreased (蠂 ~ 24.182). There was no significant correlation between COX-2 expression and age, sex, smoking history, tumor differentiation, clinical stage and EGFR gene mutation type (P0.05). There was no significant correlation between p53 expression and COX-2 expression. After EGFR-TKI treatment, the median PFS of p53 negative group and positive group were 12.0 and 7.5 months, respectively. The difference was statistically significant (蠂 ~ 24.726). The median PFS of COX-2 negative group and positive group were 12.0 and 10.0 months, respectively, and the difference was statistically significant (蠂 ~ 2 ~ (5.578) P = 0.018). The multivariate Cox proportional risk regression analysis showed that the expression of p53 (HR=0.450,P=0.046) and COX-2 (HR=0.424,P=0.021) were independent factors of PFS in patients with EGFR mutant late stage lung adenocarcinoma. Conclusion the expression of p53 and COX-2 in EGFR mutant late stage lung adenocarcinoma may promote the progression of the tumor and may be a predictor of the curative effect of EGFR-TKI.
【作者单位】：郑州大学第二附属医院肿瘤科;
【分类号】：R734.2

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