CASP3与Cleaved-CASP3在肺癌中的表达及意义

Expression and significance of CASP3 and C-CASP3 in lung cancer

目的:探讨凋亡信号分子CASP3、C-CASP3在肺癌与癌旁中的表达差异及其与临床参数的关系意义。方法:制备非小细胞肺癌患者的癌与癌旁组织石蜡标本的组织芯片。采用免疫组织化学方法检测分析CASP3、C-CASP3凋亡分子在组织中的蛋白表达水平。结果:非配对的癌(n=139)与癌旁组织(n=25)中凋亡相关分子表达水平:非参数秩和检验结果提示CASP3、C-CASP3两组间比较发现在癌组织均有显著性差异的升高表达(P<0.01);双变量相关分析显示CASP3与C-CASP3之间相关性存在统计学显著性意义。凋亡分子表达与临床病理、生存因素之间的关系:C-CASP3在非鳞癌中表达高于鳞癌(P<0.05);KaplanMeir生存曲线法分析提示Ⅰ～Ⅱ期患者中CASP3表达水平与PFS存在负相关趋势(P=0.094)。结论:肺癌组织较癌旁组织凋亡分子表达均上调,CASP3可能成为可进行药物干预的分子标志物和靶点。C-CASP3在非鳞癌中表达高于鳞癌,在非鳞癌组织类型亚群患者中CASP3更可能作为潜在的干预靶点激活为C-CASP3而促进肿瘤细胞凋亡。CASP3可能是PFS的独立预后因子。

Objective To investigate the differential expressions of the apoptotic signal molecules CASP3 and Cleaved-CASP3 （C-CASP3） in lung carcinoma and para-carcinoma tissues, and to analyze its relationship and significance with clinical parameters. Methods The tissue microarray （TMA） of paraffin specimens from lung carcinoma and para-carcinoma tissues in patients with non-small cell lung cancer （NSCLC） were made. The expression levels of CASP3 and C-CASP3 were measured by immunohistochemistry （IHC） method. Results CASP3 and C-CASP3 in carcinoma tissues （n = 139 cases） expressed much higher than in non paired para-carcinoma tissues （25 cases）,by non-parametric rank test and bivariate correlation analysis （P 〈 0.01 ）. C-CASP3 expressed higher in non-squamous cell carcinoma （non-SCC） than that in squamous cell carcinoma （P 〈 0.05）. The expression levels of CASP3 in I - II stage petients were negatively correlated with PFS in Kaplan Meir survival curve （P= 0.094）. Conclusion The expressions of apoptotic molecules in lung cancer tissues were higher than in para-carcinoma tissues. C-CASP3. express higher in non-squamous cell carcinoma than in squamous carcinoma. CASP3 may become the molecular markers and targets of drug intervention NSCLC.