核苷酸结合寡聚化结构域样受体蛋白3和caspase-1表达与非小细胞肺癌患者疾病进展的关系

Correlations of NLRP3and caspase-1levels with the progression of non-small cell lung cancer

目的观察非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)及血清caspase-1的表达情况,探讨其与NSCLC患者疾病进展的关系。方法252例NSCLC患者采用吉西他滨+顺铂方案化疗2个周期后进行疗效评估,对达临床控制的125例患者随访2年,根据有无进展(或死亡)分为进展组102例和无进展组23例。比较2组外周血NLRP3表达及血清caspase-1、P53、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平;绘制ROC曲线,评估外周血NLRP3表达及血清caspase-1水平预测NSCLC患者经吉西他滨+顺铂方案化疗临床控制后疾病进展的效能;采用Cox回归分析外周血NLRP3表达及血清caspase-1水平对经吉西他滨+顺铂方案化疗临床控制的NSCLC患者疾病进展的影响。结果进展组外周血NLRP3mRNA相对表达量[2.00(1.92,4.02)]及血清caspase-1[296.56(263.52,360.75)ng/L]、P53[8.12(6.32,9.41)u/mL]、VEGF[398.13(341.12,426.59)ng/L]水平均高于未进展组[1.36(0.86,1.75)、196.56(141.11,211.32)ng/L、3.68(3.12,4.87)u/mL、289.42(245.16,311.32)ng/L](P<0.05)。NLRP3mRNA、caspase-1分别以1.361、143.215ng/L最佳截断值,预测疾病进展的AUC分别为0.859(95%CI:0.771~0.947,P<0.001)、0.851(95%CI:0.751~0.951,P<0.001);外周血NLRP3mRNA相对表达量≥1.361、caspase-1≥143.215ng/L是NSCLC经吉西他滨+顺铂方案化疗临床控制后疾病进展的独立危险因素(OR=2.696,95%CI:1.627~5.468,P<0.001;OR=3.377,95%CI:2.034~5.606,P<0.001)。结论NSCLC患者经吉西他滨+顺铂方案化疗临床控制后疾病进展可能与外周血NLRP3及血清caspase-1过表达有关,NLRP3、caspase-1对预测疾病进展、指导NSCLC的治疗及改善患者预后有重要作用。

Objective To analyze the relationships of the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in peripheral blood and serum caspase-1level with the disease progression by observing the expressions of NLRP3and caspase-1in patients with non-small cell lung cancer(NSCLC).Methods Totally 252patients with NSCLC received GP(gemcitabine+cisplatin)regimen chemotherapy and their efficacies were evaluated after 2 cycles,in which 125patients reached the clinical control and were divided into progressive group(n=102)and non-progressive group(n=23)according to 2-year follow-up result.The expressions of NLRP3in peripheral blood and the serum levels of caspase-1,P53and vascular endothelial growth factor(VEGF)were compared between two groups.ROC was drawn to evaluate the efficacies of NLRP3and caspase-1on predicting the progression of NSCLC after GP chemotherapy.COX regression analysis was used to assess the effects of NLRP3and caspase-1on the progression of NSCLC in patients responding to GP chemotherapy.Results The levels of NLRP3mRNA,caspase-1,P53and VEGF were higher in progression group(2.00(1.92,4.02),296.56(263.52,360.75)ng/L,8.12(6.32,9.41)u/mL,398.13(341.12,426.59)ng/L)than those in non-progressive group(1.36(0.86,1.75),196.56(141.11,211.32)ng/L,3.68(3.12,4.87)u/mL,289.42(245.16,311.32)ng/L)(P<0.05).When the optimal cut-off values of NLRP3mRNA and caspase-1were 1.361and 143.215ng/L,the AUCs for predicting the disease progression were 0.859(95%CI:0.771-0.947,P<0.001)and 0.851(95%CI:0.751-0.951,P<0.001).NLRP3mRNA≥1.361and caspase-1≥143.215ng/L were the independent risk factors of progression of NSCLC in patients responding to GP chemotherapy(OR=2.696,95%CI:1.627-5.468,P<0.001;OR=3.377,95%CI:2.034-5.606,P<0.001).Conclusion The progression of NSCLC after GP chemotherapy may be correlated with the overexpressions of NLRP3in peripheral blood and serum caspase-1.The detection of NLRP3 and caspase-1 levels of patients with NSCLC contributes to the prediction of disease progression after chemotherapy,the guidance of the treatment of NSCLC and the improvement of prognosis.