摘要
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.
作者
何秋蓉
杨天通
叶波
HE Qiu-rong;YANG Tian-tong;YE Bo(Department of Laboratory Medicine,West China School of Public Health of Sichuan University,West China Fourth Hospital of Sichuan University,Chengdu,Sichuan 610041,China;Department of Laboratory Medicine,Sichuan Cancer Hospital,Chengdu,Sichuan 610041,China)
出处
《中华实用诊断与治疗杂志》
2021年第3期264-267,共4页
Journal of Chinese Practical Diagnosis and Therapy
基金
四川省卫生和计划生育委员会科研课题(16PJ256)。