血清miR-25和miR-100作为食管鳞状细胞癌诊断和预后标志物研究

Study on Serum miR-25 and miR-100 as Diagnostic and Prognostic Markers for Esophageal Squamous Cell Carcinoma

目的 探讨血清miR-25和miR-100对食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）的诊断和预后价值.方法 收集2011年6月～2014年5月南京军区南京总医院及徐州市肿瘤医院63例ESCC患者术前、术后及随访血清,并收集63例年龄、性别匹配的非癌健康人血清作为对照;实时荧光定量PCR法检测血清miR-25和miR-100含量.用非参数Mann-Whitney U检验ESCC患者组和对照组血清miR-25和miR-100表达水平的差异,配对t检验分析ESCC患者术前术后血清中miR-25和miR-100的表达量变化,受试者工作特征曲线（ROC）评估血清miR-25和miR-100对ES-CC的诊断价值,单因素Kaplan-Meier法分析对ESCC患者生存的影响.结果 与健康对照相比,ESCC患者血清miR-25（0.40±0.20 vs 0.02±0.01）和miR-100的相对含量（0.10±0.02 vs 0.04±0.00）显著升高,差异具有统计学意义（U值分别为885.0和1 006.0,P值均＜0.01）;血清miR-25和miR-100的ROC曲线下面积AUC均明显大于癌胚抗原;ESCC患者术后血清miR-100含量较术前明显降低（0.07±0.01 vs 0.10±0.02）,差异具有统计学意义（t=2.367,P=0.021）;单因素Kaplan-Meier法分析显示血清miR-25和miR-100表达阴性的ESCC患者的生存期明显高于阳性患者（P＜0.05）.结论 血清miR-25和miR-100可作为ESCC诊断及预后评估的潜在标志物.

Objective To investigate the diagnostic and prognostic values of serum miR-25 and miR-100 for esophageal squa- mous cell carcinoma（ESCC）. Methods Serum samples were collected from 63 ESCC patients before and after surgery in Nanjing General Hospital and Xuzhou Cancer Hospital between June 2013 and May 2014. In the meanwhile, serum samples were collected from 63 age- and sex-matched individuals as non-cancer controls. Quantitative real-time PCR was used to de- tect the serum concentrations of miR-25 and miR-100. The nonparametric Mann-Whitney U-test was used to analyze the differences of miR-25 or miR-100 levels hetween ESCC patients and controls. Paired t test was used to analyze the differ- ences of serum miR-25 or miR-100 levels of pre-or postoperative ESCC patients. ROC curve analysis was conducted to evalu- ate the diagnostic value of serum miR-25 and miR-100 for ESCC. Univariate Kaplan-Meier analysis was applied to assess the prognostic value of serum miR-25 and miR-100 on the survival of patients with ESCC. Results Compared with controls, ser- um levels of miR-25 and miR-100 in ESCC patients were significantly increased （0.40 ± 0.20 vs 0.02 ± 0.01 ,U= 885.0, P〈 0. 01;0.10±0. 02 vs 0.04± 0.00,U= 1 006, P〈0.01, respectively）. ROC curve analysis showed that the areas under the ROC curves of serum miR-25 and miR-100 for ESCC were larger than that of carcinoembryonic antigen. Serum miR-100 was significantly declined in postoperative ESCC patients as compared to preoperative patients （0.07±0.01 vs 0.10±0.02,t= 2. 367,P=0. 021）. Univariate Kaplan-Meier analysis showed that ESCC patients with low levels of miR-25 and miR-100 in their serum exhibited higher survival rates than those with high levels. Conclusion Serum miR-25 and miR-100 could be used as potential diagnostic and prognostic markers of ESCC.