血清microRNA对食管鳞癌同步放化疗近期疗效预测价值分析

Analysis the predictive value of serum microRNA in the efficacy of radiochemotherapy on locally advanced esophageal squamous cell carcinoma patients

目的同期放化疗是局部晚期食管鳞癌的推荐治疗方案,目前尚无明确预测食管鳞癌放化疗疗效的血清分子标志物。本研究通过对局部晚期食管鳞癌放化疗疗效的血清微小RNA(micoRNA,miRNA)的筛选验证及分析,探讨血清microRNA与食管鳞癌放化疗近期疗效的关系及疗效预测价值。方法新疆医科大学第一附属医院2015-01-01-2016-06-30收治的Ⅲ~Ⅳ期食管鳞癌患者30例,进行同步放化疗,同时采集患者放化疗前后外周血,根据RECIST 1.1标准评价近期疗效,分为敏感组和抗拒组;用Agilent miRNA人类基因芯片进行两组血清miRNA检测及实时荧光定量聚合酶链反应法(quantitative real-time PCR,qRT-PCR)定量验证,分析筛选并验证的miRNA和放化疗近期疗效的关系,受试者工作特征(receiver operating characteristic,ROC)曲线评价miRNA近期疗效预测价值。结果 30例患者经过同期放化疗后,敏感组14例,抵抗组16例。两组患者血清共筛查了11个miRNA差异表达,其中miR-623、miR-5703及miR-483-5p经qRT-PCR验证后差异有统计学意义。分别以miR-623、miR-5703及miR-483-5p在各组相对表达量的均值为分界线分为高表达和低表达,敏感组和抵抗组的miR-623高表达率分别为28.0%和62.5%,χ2=4.858,P=0.040;miR-5703高表达率分别为12.0%和62.5%,χ2=7.423,P=0.005。敏感组miR-483-5p低表达率为34.0%,低于治疗抗拒组的81.3%,差异有统计学意义,χ2=6.151,P=0.018。ROC曲线预测miR-623与食管鳞癌放化疗近期疗效的曲线下面积(area under curve,AUC)、灵敏度和特异度分别为0.809、72.2%和82.0%,miR-5703分别为0.928、91.7%和90.0%,miR-483-5p分别为0.838、69.4%和90.0%。结论局部晚期食管鳞癌患者血清中可以筛查到与放化疗疗效相关的miRNA,miR-623、miR-5703和miR-483-5p对于食管鳞癌放化疗近期疗效可能具有预测价值。

OBJECTIVE There are no serum molecular markers that can predict the efficacy of chemoradiotherapy in esophageal squamous cell carcinoma.This thesis was to verify and analyze the serum micoRNA,the treatment markers of partial advanced esophageal squamous cell carcinoma,and to explore the correlation between serum microRNA and shortterm efficacy of esophageal squamous cell carcinoma as well as the serum microRNA＇s efficacy predictive value to this carcinoma.METHODS A total of 30 patients with stageⅢ-Ⅳ esophageal squamous cell carcinoma who were admitted to the First Affiliated Hospital of Xinjiang Medical University from January 1,2015 to June 30,2016 were included to be conducted with concurrent radiotherapy and chemotherapy.In the meantime,their peripheral blood were collected before and after the chemoradiotherapy,and then they were divided into the sensitive group and the resistant group according to RECIST 1.1 standard about short-term efficacy evaluation;a serum microRNA examination and a quantitative qRT-PCR validation with agilent microRNA human gene chips were made to finally analyze,screen and verify the relationship between microRNA and the short-term efficacy of radiotherapy and chemotherapy.The predictive value of micoRNA about the short-term efficacy was to be estimated by ROC curve.RESULTS After the concurrent radiotherapy and chemotherapy in 30 patients,a total of 14 patients in the sensitive group and 16 patients in the resistant group were treated.There was no difference of age,gender,histological grade,site and clinical stage between the two groups and was statistically significant（P〉0.05）.A total of 11 microRNAs were differentially expressed in the serum from the two groups,among which the differences between miR-623,miR-5703 and miR-483-5 p were still statistically significant after validation of qRT-PCR.The mean value of relative expression volume of miR-623,miR-5703 and miR-483-5 p in each group was treated as the divisional standard to high and low expression levels.The high expression rates of miR-623 and miR-5703 in the sensitive group were 28.0% and 12.0%,which were lower than 62.5% and 62.5%in the resistant group.The above differences were statistically significant（χ^2=4.858,7.423,P=0.040,0.005）.The low expression rate of miR-483-5 p was 34.0%in the sensitive group,which was lower than that of 81.3%in the resistant group.The above difference was statistically significant（χ^2=6.151,P=0.018）.Under the prediction of ROC curve,among the correlation of miR-623 and the short-term efficacy of radiotherapy and chemotherapy for esophageal squamous cell carcinoma,the area under the curve（AUC）,sensitivity and specificity were 0.809,72.2% and 82.0% respectively;those of miR-5703 were 0.928,91.7% and 90.0% respectively;and those of miR-483-5 p were 0.838,69.4% and 90.0%respectively.CONCLUSIONS The microRNA,which is correlated with radiotherapy and chemotherapy efficacy,can be screened in the serum of patients with partial advanced esophageal squamous cell carcinoma;miR-623,miR-5703 and miR-483-5 p may have predictive value for the short-term efficacy of radiotherapy and chemotherapy for esophageal squamous cell carcinoma.