恶性胸腔积液细胞游离miR-130a与非小细胞肺癌患者生存的关系

Correlation between cell-free miR-130a in malignant pleural effusion and survival of patients with non-small cell lung cancer

目的:分析恶性胸腔积液(MPE)中细胞游离miRNAs的表达及其与非小细胞肺癌(NSCLC)患者生存预后的关系。方法:收集2016年3月至2020年12月本院92例NSCLC患者的MPE样本,中位生存期为6个月,随机选择5例生存期≤6个月的患者和5例生存期>6个月的患者,进行细胞游离miRNAs微阵列分析。使用定量RT-qPCR法对92例患者MPE样本进行miRNAs表达验证。采用单因素和多因素Cox比例风险回归模型分析生存预测因素。结果:在生存期≤6个月和生存期>6个月患者的MPE中,有33个miRNAs在微阵列中差异表达超过2倍,其中5个miRNAs表达水平(miR-130a、miR-345、miR-100、miR-24和miR-93)与总生存期显著相关。低miR-130a水平(中位值0.51)、低miR-100水平(中位值0.09)均与NSCLC患者较短的中位生存时间有关(P<0.05)。多因素Cox回归分析显示:年龄(P=0.020)、miR-130a(P=0.001)和吸烟史(P=0.001)均为NSCLC患者生存的独立预测因素。结论:胸腔积液中miR-130a可以作为NSCLC患者总生存期的候选预测指标之一。

Objective:To analyze the expression of cell-free miRNAs in malignant pleural effusion(MPE)and its relationship with the survival and prognosis of patients with non-small cell lung cancer(NSCLC).Methods:MPE samples were collected from 92 NSCLC patients in our hospital from March 2016 to December 2020,with a median survival time of 6 months.Five patients with survival≤6 months and five patients with survival>6 months were randomly selected for cell-free miRNAs microarray analysis.The expression of miRNAs in 92 MPE samples was verified by quantitative real-time reverse transcription-quantitative PCR(RT-qPCR).Quantitative RT-PCR was used to verify the expression of miRNAs in 92 MPE patients.Univariate and multivariate Cox proportional hazard regression models were used to analyze the survival predictors.Results:Among MPE patients with survival period≤6 months and survival period>6 months,33 miRNAs were differentially expressed more than twice in microarray,among which 5 miRNAs expression levels(miR-130a,miR-345,miR-100,miR-24 and miR-93)were significantly correlated with overall survival.Both low miR-130a level(median 0.51)and low miR-100 level(median 0.09)were all related to the shorter median survival time of NSCLC patients(P<0.05).Multivariate Cox regression analysis showed that the age(P=0.020),miR-130a(P=0.001)and smoking history(P=0.001)were independent predictors of NSCLC patient survival.Conclusion:miR-130a in pleural effusion can be used as an effective predictor of the overall survival of NSCLC patients.