肺癌患者血清miRNA-4534水平和病理分期与预后的关系

Relationship between serum miRNA-4534 level and pathological staging and prognosis of patients with lung cancer

目的探讨肺癌患者血清微小核糖核苷酸(miRNA)-4534水平和病理分期与预后的关系。方法选取2014年1月至2016年6月间收治的64例肺癌患者(肺癌组)作为研究对象,并纳入30例良性肺病患者(良性肺病组)和30例体检健康志愿者作为对照组。采集受试者外周血,采用实时荧光定量聚合酶链式反应(q RT-PCR)检测血清miRNA-4534的相对表达量,绘制受试者工作特征(ROC)曲线评估miRNA-4534诊断肺癌效能,分析miRNA-4534与肺癌患者病理特征的关系。随访3年,评估miRNA-4534与肺癌患者预后的关系。结果肺癌组miRNA-4534相对表达量高于良性肺病组和对照组,差异有统计学意义(P<0.05);良性肺病组和对照组miRNA-4534相对表达量对比,差异无统计学意义(P>0.05);ROC曲线显示,miRNA-4534诊断肺癌发病的曲线下面积(AUC)为0.839(95%CI:0.777~0.931,P<0.05),最佳临界值为2.52,敏感性76.56%,特异性98.33%;不同性别、年龄、吸烟史、肿瘤大小、病理类型间miR-4534相对表达量比较,差异均无统计学意义(P>0.05),TNMⅢ/Ⅳ期肺癌患者miR-4534相对表达量高于Ⅰ/Ⅱ期者,差异有统计学意义(P<0.05);有淋巴结转移肺癌患者miR-4534相对表达量高于无淋巴结转移者,差异有统计学意义(P<0.05);随访3年,获得随访资料者62例患者、生存率40.32%(25/62),总生存时间(26.27±9.92)个月;miR-4534高表达组3年生存率、生存时间均低于低表达组,差异有统计学意义(P<0.05);miRNA-4534诊断预后不良AUC为0.914(95%CI:0.814~0.970,P<0.05),最佳临界值为15.69;miRNA-4534水平与肺癌患者生存期呈负相关关系(P<0.05)。结论血清miRNA-4534与肺癌发生、进展均相关,且是预测患者预后的有效指标。

Objective To investigate the relationship between serum micro-ribonucleotide(miRNA)-4534 level and pathological staging and prognosis of patients with lung cancer.Methods Sixtyfour patients with lung cancer(lung cancer group)who were treated between January 2014 and June 2016 were selected as the research subjects.Thirty patients with benign lung disease(benign lung disease group)and thirty healthy volunteers with physical examination(control group)were included.The peripheral blood of the subjects was collected,and the relative expression level of serum miRNA-4534 was detected by real-time fluorescent quantitative polymerase chain reaction(qRT-PCR).The receiver operating characteristic(ROC)curve was plotted to evaluate the efficacy of miRNA-4534 in the diagnosis of lung cancer.Relationship between miRNA-4534 and pathological features in patients with lung cancer was analyzed.At 3 years of follow-up,the relationship between miRNA-4534 and prognosis of patients with lung cancer was evaluated.Results The relative expression level of miRNA-4534 in the lung cancer group was higher than that in the benign lung disease group and the control group,the difference was statistically significant(P<0.05),and there was no significant difference in the relative expression level of miRNA-4534 between the benign lung disease group and the control group,the difference was not statistically significant(P>0.05).ROC curve showed that the area under the curve(AUC),optimal cut-off value,sensitivity and specificity of miRNA-4534 in the diagnosis of occurrence of lung cancer were 0.839(95%CI:0.777~0.931,P<0.05),2.52,76.56%and 98.33%.There was no significant difference in the relative expression level of miR-4534 among patients with different gender,age,smoking history,tumor size and pathological type(P>0.05).The relative expression level of miR-4534 of patients with TNM stageⅢ/Ⅳlung cancer was higher than that of patients with stageⅠ/Ⅱ,and the difference was statistically significant(P<0.05),and the relative expression level of miR-4534 of patients with lymph node metastasis was higher than that of patients without lymph node metastasis(P<0.05).At 3 years of followup,there were 62 patients with follow-up data,and the survival rate and overall survival time were 40.32%(25/62)and(26.27±9.92)months.The 3-year survival rate and survival time of miR-4534 high expression group were lower than those of low expression group,the difference was statistically significant(P<0.05).The AUC of miRNA-4534 in the diagnosis of poor prognosis was 0.914(95%CI:0.814-0.970,P<0.05),and the optimal cutoff value was 15.69.The level of mirNA-4534 was negatively correlated with the survival time of patients with lung cancer(P<0.05).Conclusion Serum miRNA-4534 is related to the occurrence and progression of lung cancer and is an effective indicator for predicting the prognosis of patients.