血清外泌体lncRNA PCGEM1、miR-129-5p与非小细胞肺癌患者临床病理特征及预后的关系

摘要 目的：研究血清外泌体长链非编码核糖核酸（lncRNA）前列腺癌基因表达标记1（PCGEM1）、微小核糖核酸（miR）-129-5p与非小细胞肺癌（NSCLC）患者临床病理特征及预后的关系。方法：选取2016年2月-2018年1月南京脑科医院收治的125例NSCLC患者作为NSCLC组，同期选取体检的70例健康人群作为健康组。采集两组静脉血，提取血清外泌体；采用实时定量聚合酶链式反应（qRT-PCR）检测血清外泌体lncRNA PCGEM1、miR-129-5p表达情况；采用Pearson相关性分析lncRNA PCGEM1与miR-129-5p的关系。并分析血清外泌体lncRNA PCGEM1、miR-129-5p与NSCLC患者临床病理特征的关系。对NSCLC患者行5年随访，绘制Kaplan-Meier曲线分析预后情况，多因素Cox比例风险回归模型分析预后不良危险因素，受试者工作特征（ROC）曲线分析lncRNA PCGEM1、miR-129-5p对NSCLC预后的预测价值。结果：：NSCLC组lncRNA PCGEM1相对表达量高于健康组，miR-129-5p相对表达量低于健康组（P＜0.05）。血清外泌体lncRNA PCGEM1相对表达量与miR-129-5p表达呈负相关（r= -0.420，P＜0.05）。血清外泌体lncRNA PCGEM1、miR-129-5p表达与患者TNM分期、分化程度、淋巴结转移有关（P＜0.05）。Kplan-Meier生存曲线显示，lncRNA PCGEM1低表达组5年生存率69.05%高于lncRNA PCGEM1高表达组35.53%，miR-129-5p高表达组5年生存率68.09%高于miR-129-5p低表达组33.80%。多因素Cox比例风险回归显示，TNM分期III期、有淋巴结转移、lncRNA PCGEM1高表达、miR-129-5p低表达为NSCLC患者预后不良的独立危险因素（P＜0.05）。ROC曲线显示，lncRNA PCGEM1、miR-129-5p联合检测对NSCLC预后的预测曲线下面积（AUC）为0.865，预测价值高于两者单独预测。结论：NSCLC患者血清外泌体lncRNA PCGEM1表达上调、miR-129-5p表达下调，二者表达与NSCLC患者TNM分期、分化程度、淋巴结转移有关，且与患者预后密切相关，对NSCLC预后不良具有较好预测价值。

Relationship between Serum Exosomes lncRNA PCGEM1, miR-129-5p and Clinical Pathological Characteristics and Prognosis of Patients with Non-Small Cell Lung Cancer

ABSTRACT Objective: To study the relationship between serum exosomes long non-coding ribonucleic acid (lncRNA) prostate cancer gene expression marker 1 (PCGEM1), micro ribonucleic acid (miR)-129-5p and clinical pathological characteristics and prognosis of patients with non-small cell lung cancer (NSCLC). Methods: 125 patients with NSCLC who were admitted to Nanjing Brain Hospital from February 2016 to January 2018 were selected as NSCLC group, 70 healthy individuals who were underwent physical examinations were selected as health group during the same period. The venous blood were collected of two groups, and the serum exosomes were extracted. The expression of serum exosomes lncRNA PCGEM1 and miR-129-5p were detected by the real time quantitative polymerase chain reaction (qRT-PCR). The relationship between lncRNA PCGEM1 and miR-129-5p was analysed by Pearson correlation. And the relationship between serum exosomes lncRNA PCGEM1, miR-129-5p and clinical pathological characteristics of patients with NSCLC was analyzed. 5 years followed up for patients with NSCLC, the prognosis was analyzed by plotted Kaplan-Meier curve, the risk factors for poor prognosis were analyzed by multivariate Cox proportional risk regression model, and the predictive value of lncRNA PCGEM1 and miR-129-5p of predicted the NSCLC prognosis was analyzed by the receiver operating characteristic (ROC) curve. Results: The relative expression level of lncRNA PCGEM1 of NSCLC group was higher than that of healthy group, while the relative expression level of miR-129-5p was lower than that of healthy group (P<0.05). The relative expression level of serum exosomes lncRNA PCGEM1 was negatively correlated with the expression of miR-129-5p (r=-0.420, P<0.05). The expression of serum exosomes lncRNA PCGEM1 and miR-129-5p were related to TNM stage, differentiation degree, and lymph node metastasis of patients(P<0.05). The Kplan-Meier survival curve showed that the 5 years survival rate of lncRNA PCGEM1 low expression group was 69.05% higher than 35.53% of lncRNA PCGEM1 high expression group, and the 5 years survival rate of miR-129-5p high expression group was 68.09% higher than 33.80% of miR-129-5p low expression group. Multivariate Cox proportional risk regression showed that TNM stage III, lymph node metastasis, high expression of lncRNA PCGEM1, and low expression of miR-129-5p were independent risk factors for poor prognosis of patients with NSCLC (P<0.05). ROC curve showed that the area under the curve (AUC) of predicted the NSCLC prognosis by the combined detection of lncRNA PCGEM1 and miR-129-5p was 0.865, and the predictive value was higher than both separately predicted. Conclusion: The expression of serum exosomes lncRNA PCGEM1 of patients with NSCLC is upregulated, while the expression of miR-129-5p is downregulated, the expression of both is related to TNM stage, differentiation degree, and lymph node metastasis of patients with NSCLC, and closely related to patient prognosis, which has good predictive value for poor prognosis of NSCLC.