【摘要】：目的針對(duì)表皮生長(zhǎng)因子受體(epidermal growth factor receptor,EGFR)敏感突變的酪氨酸激酶抑制劑(tyrosine kinase inhibitor,TKI)治療已成為肺癌精準(zhǔn)治療的典范,但多數(shù)患者在EGFR-TKI治療有效后的8~16個(gè)月不可避免會(huì)出現(xiàn)獲得性耐藥。本研究探討p53和COX-2在EGFR突變型晚期肺腺癌組織中的表達(dá)及其與患者臨床特征的關(guān)系,并觀察其表達(dá)對(duì)EGFR-TKI療效的影響。方法選取2014-03-01-2016-01-31于鄭州大學(xué)第二附屬醫(yī)院病理確診為EGFR突變型晚期肺腺癌并接受EGFR-TKI治療的43例患者,利用免疫組織化學(xué)法檢測(cè)p53和COX-2在EGFR突變型晚期肺腺癌組織中的表達(dá);χ~2檢驗(yàn)分析其與臨床特征之間的相關(guān)性;生存分析采用Kaplan-Meier法;并進(jìn)一步對(duì)影響患者無(wú)進(jìn)展生存期(progression-free survival,PFS)的因素采用Cox比例風(fēng)險(xiǎn)回歸模型分析。結(jié)果 43例EGFR突變型晚期肺腺癌患者中,p53、COX-2表達(dá)陽(yáng)性率分別為41.8%和53.4%。p53表達(dá)隨年齡增長(zhǎng)(χ~2=3.939,P=0.047)及腫瘤分化程度減低(χ~2=4.182,P=0.041)而升高。COX-2表達(dá)與年齡、性別、吸煙史、腫瘤分化程度、臨床分期及EGFR基因突變類型均未見(jiàn)明顯相關(guān)性(P0.05)。p53與COX-2表達(dá)無(wú)明顯相關(guān)性,P0.05�；颊呓邮蹺GFR-TKI治療后,p53陰性組和陽(yáng)性組中位PFS分別為12.0和7.5個(gè)月,差異有統(tǒng)計(jì)學(xué)意義,χ~2=4.726,P=0.030;COX-2陰性組和陽(yáng)性組中位PFS分別為12.0和10.0個(gè)月,差異有統(tǒng)計(jì)學(xué)意義,χ~2=5.578,P=0.018。進(jìn)一步行多因素Cox比例風(fēng)險(xiǎn)回歸模型分析顯示,p53(HR=0.450,P=0.046)和COX-2(HR=0.424,P=0.021)表達(dá)均為EGFR突變型晚期肺腺癌患者PFS的獨(dú)立影響因素。結(jié)論 EGFR突變型晚期肺腺癌組織中,p53和COX-2表達(dá)可能促進(jìn)腫瘤進(jìn)展,有望成為EGFR-TKI療效的預(yù)測(cè)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.
【作者單位】： 鄭州大學(xué)第二附屬醫(yī)院腫瘤科;
【分類號(hào)】：R734.2

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