非小细胞肺癌组织中miR-219和环氧合酶-2表达水平联合预测新辅助化疗患者预后的价值

目的：探讨非小细胞肺癌(NSCLC)组织中微小核糖核苷酸-219(miR-219)和环氧合酶-2(COX-2)表达水平联合预测新辅助化疗患者预后的价值。方法采用免疫组化法检测2009年1月至2012年1月期间我院应用纤维支气管镜活检所得的85例NSCLC组织(NSCLC组)、30例肺部良性病变组织(良性组)和30例正常肺组织（正常组)中miR-219和COX-2蛋白的表达水平。统计NSCLC组患者无疾病进展生存期(3年生存率)，比较不同miR-219和COX-2蛋白患者的3年生存率，分析NSCLC组织中miR-219和COX-2蛋白水平与其3年生存率的关系及两者联合预测新辅助化疗患者预后的价值。结果 NSCLC组miR-219蛋白阳性表达率为48.24%，低于良性组和正常组的73.33%和80.00%，COX-2蛋白阳性水平为61.18%，高于良性组和正常组的20.00%和16.67%，差异均有统计学意义(P<0.05)，而良性组和正常组中miR-219和COX-2蛋白阳性表达水平比较差异无统计学意义(P>0.05)；NSCLC组患者3年生存率为44.71%，且miR-219蛋白阴性表达患者和COX-2蛋白阳性表达患者的3年生存率低于miR-219蛋白阳性表达患者和COX-2蛋白阴性表达患者(P<0.05)。Spearman秩相关分析结果显示， miR-219蛋白阳性表达水平与NSCLC新辅助化疗患者3年生存率呈正相关(r=0.784，P<0.05)；COX-2蛋白阳性表达率与NSCLC新辅助化疗患者3年生存率则呈负相关(r=-0.783，P<0.05)。ROC曲线分析结果显示，NSCLC新辅助化疗患者miR-219和COX-2蛋白表达联合预测患者的预后的灵敏度、特异度、准确性、曲线下面积、阳性预测值和阴性预测值分别为97.37%、95.74%、96.47%、0.775、94.87%和97.83%。结论 NSCLC新辅助化疗患者miR-219蛋白阳性表达率下降而COX-2蛋白阴性表达率上升，且两者联合预测患者预后的价值良好，miR-219和环氧合酶-2表达水平可能作为NSCLC新辅助化疗患者预后评估的参考指标。

Value of combined detection of miR-219 and cyclooxygenase-2 in predicting prognosis of patients with non-small cell lung cancer treated with neoadjuvant chemotherapy

Objective To explore the value of tiny ribonucleotid-219 (MiR-219) and cyclooxygenase-2 (COX-2) expression level in predicting prognosis of patients with non-small cell lung cancer (NSCLC) treated with neo-adjuvant chemotherapy. Methods Eighty-five NSCLC tissue samples (NSCLC group), 30 lung benign lesion tissue samples (benign group) and 30 normal lung tissue samples (normal group) were obtained by fiberoptic bronchoscopy in our hospital from January 2009 to January 2012, and miR-219 and the COX-2 protein expression level of the three groups were detected by immunohistochemical method. The 3-year survival rates of NSCLC group were statistically an-alyzed, and the 3-year survival rates of patients with different levels of miR-219 and COX-2 protein were compared. Relationship between miR-219, COX-2 protein expression levels in NSCLC tissue samples and its 3-year survival rate were analyzed. The value of miR-219 and COX-2 protein expression levels in predicting prognosis of NSCLC patients treated with neoadjuvant chemotherapy were also analyzed. Results The positive expression rate of miR-219 protein in NSCLC group was 48.24%, which was significantly lower than 73.33%of benign group and 80.00%of normal group, while positive expression rate of COX-2 protein (61.18%) was significantly higher than that of benign group and nor-mal group (20.00% and 16.67%), with statistically significant differences (P<0.05). The positive expression level of miR-219 and COX-2 protein had no statistically significant difference between benign group and normal group (P>0.05). The 3-year survival rate of NSCLC group was 44.71%, and the patients with negative expression of miR-219 and those with positive expression of COX-2 protein had lower 3-year survival rate than the patients with positive expres-sion of miR-219 and negative expression of COX-2 protein (P<0.05). Spearman rank correlation analysis showed that positive expression level of miR-219 protein and 3-year survival rates of NSCLC patients treated with neoadjuvant che-motherapy were positively correlated (r=0.784, P<0.05), while positive expression rate of COX-2 protein and 3-year sur-vival rates of NSCLC patients treated with neoadjuvant chemotherapy were negatively correlated (r=-0.783, P<0.05). ROC curve analysis showed that the sensitivity, specificity, accuracy, area under the curve, positive predictive value and negative predictive value of miR-219 and COX-2 protein expression levels in predicting prognosis of NSCLC patients treated with neoadjuvant chemotherapy were 97.37%, 95.74%, 96.47%, 0.775, 94.87%and 97.83%respectively. Conclusion NSCLC patients treated with neoadjuvant chemotherapy had lower miR-219 protein posi-tive expression rate and higher COX-2 protein negative expression rate, and combined detection of miR-219 and COX-2 protein negative has high value in predicting prognosis of NSCLC patients treated with neoadjuvant chemothera-py. The expression levels of miR-219 and COX-2 may be taken as reference index for evaluating the prognosis of NSCLC patients treated with neoadjuvant chemotherapy.