摘要
目的 探讨微小RNA(miR)-15b、miR-29a、miR-30a、miR-449a在早期肺腺癌血浆中的表达及与胸腔镜术后复发的相关性.方法 纳入早期肺腺癌患者102例(研究组)及健康志愿100例(对照组).根据研究组患者例数的中位数将其分别分为miR-15b、miR-29a、miR-30a、miR-449a高、低表达组共8组.根据术后2年内是否复发将研究组再分为复发组(34例)及未复发组(68例).收集所有受试者一般资料、血浆中miR-15b、miR-29a、miR-30a、miR-449a表达水平及研究组临床病例资料(肿瘤组织分化程度、临床分期及淋巴结转移情况)和胸腔镜根治术后2年内复发情况并分组进行比较.影响因素分析采用单因素及多因素logistic回归分析.采用受试者工作特征(ROC)曲线判定不同miRNA对早期肺腺癌及其胸腔镜术后复发的诊断价值.结果 与对照组比较,研究组受试者血浆miR-15b、miR-30a、miR-449a表达水平均明显降低,而miR-29a表达水平明显升高(P＜0.05).miR-15b、miR-30a、miR-449a低表达组肿瘤组织低分化、临床分期高(ⅡA/ⅡB期)及淋巴结转移患者比例均高于对应高表达组,miR-29a高表达组肿瘤组织低分化、临床分期高(ⅡA/ⅡB期)及淋巴结转移患者比例均高于对应低表达组(P＜0.05).与未复发组相比,复发组血浆miR-15b、miR-30a、miR-449a表达水平均降低,而miR-29a表达水平升高(P＜0.05).多因素logistic回归分析结果显示,低分化程度、高临床分期、淋巴结转移、血浆miR-15b、miR-30a、miR-449a表达水平低及miR-29a表达水平高均是早期肺腺癌患者胸腔镜术后肿瘤复发的危险因素(P＜0.05).ROC曲线分析结果显示,miR-15b、miR-29a、miR-30a、miR-449a及四者联合对早期肺腺癌及其胸腔镜术后复发均有诊断价值,敏感度及特异度均较高,其中四者联合诊断的曲线下面积(AUC)均高于单一指标(P＜0.05).结论 胸腺癌患者胸腔镜根治术前测定血浆内miR-15b、miR-29a、miR-30a、miR-449a水平有助于诊断术后是否存在肿瘤复发现象,联合检测诊断效能最高.
Abstract
Objective Explore the expression of microRNA(miR)-15b,miR-29a,miR-30a,and miR-49a in the plasma of early lung adenocarcinoma and their correlation with postoperative recurrence after thoracoscopy.Methods A total of 102 patients with early lung adenocarcinoma(study group)and 100 healthy volunteers(control group)were included.According to the median number of patients in study group,they were divided into 8 groups with high and low expression of miR-15b,miR-29a,miR-30a and miR-449a,respectively.Patients in study group were divided into relapsed group(34 cases)and non-relapsed group(68 cases)according to whether recurrence occurred within 2 years after surgery.General data,the expression levels of miR-15b,miR-29a,miR-30a and miR-449a in plasma of all subjects,clinical case data(differentiation degree,clinical stage and lymph node metastasis)and recurrence within 2 years after thoracoscope radical surgery of patients in study group were collected and compared in different groups.The influence factors were analyzed by univariate and multifactorial logistic regression analysis.Receiver operating characteristic(ROC)curve was used to determine the diagnostic value of different miRNA in the diagnosis of early lung adenocarcinoma and its thoracoscopic postoperative recurrence.Results Compared with control group,the expression levels of miR-15b,miR-30a and miR-449a in plasma of subjects in study group were significantly decreased,while the expression levels of miR-29a were significantly increased(P＜0.05).The proportion of patients with tumor tissue low differentiation,high clinical stage(Ⅱ A/Ⅱ B stage)and lymph node metastasis in low expression group of miR-15b,miR-30a and miR-449a were higher than those in corresponding high expression group,the proportion of patients with tumor tissue low differentiation,high clinical stage(Ⅱ A/Ⅱ B stage)and lymph node metastasis in high miR-29a expression group was higher than those in corresponding low expression group(P＜0.05).Compared with the non-relapsed group,the expression levels of miR-15b,miR-30a and miR-449a in relapsed group were decreased,while the expression levels of miR-29a were increased(P＜0.05).Multivariate logistic regression analysis showed that low differentiation,high clinical stage,lymph node metastasis,low expression level of miR-15b,miR-30a and miR-449a in plasma and high expression level of miR-29a were all risk factors for tumor recurrence in patients with early lung adenocarcinoma after thoracoscopic surgery(P＜0.05).ROC curve analysis results showed that miR-15b,miR-29a,miR-30a,miR-449a and the combination of the four had diagnostic value for early lung adenocarcinoma and thoracoscopic postoperative recurrence,with high sensitivity and specificity(P＜0.05),and the area under the curve(AUC)of combined diagnosis was higher than that of single index in four of them.Conclusion Preoperative measurement of plasma levels of miR-15b,miR-29a,miR-30a,and miR-449a in patients with thymic cancer undergoing thoracoscopic radical surgery can help predict whether there is tumor recurrence after surgery,and the combined detection has the highest predictive efficacy.
基金项目
邯郸市科学技术研究与发展计划项目(21422083120)
NETL
NSTL
万方数据