血清miR-193a-3p,miR-337-5p和miR-483-5p在食管鳞状细胞癌诊断和预后中的应用

Application of Serum miR-193a-3p,miR-337-5p and miR-483-5p in the Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma

目的探讨miR-193a-3P,miR-337-5p和miR-483-5p在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)患者血清中的表达水平,评估其临床应用价值。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住院的63例ESCC患者术前、术后血清及随访信息,同时收集63例年龄、性别相匹配的健康体检者血清作为正常对照。利用TaqMan低密度芯片方法筛选出ESCC患者中异常表达的miRNA;实时荧光定量PCR法验证芯片检测到的ESCC中明显上调的miR-193a-3p,miR-337-5P以及文献报道在口腔鳞状细胞癌(OSCC)表达上调的miR-483-5P;最后评价它们的诊断和预后价值。结果与健康对照相比,ESCC患者血清miR-193a-3p(0.459±0.339 vs 0.195±0.084),miR-337-5p(5.686±5.211 vs 2.476±0.808)和miR-483-5p(32.545±22.479 vs 19.509±10.601)的相对含量均显著升高(U值分别为591,605和1037,P值均<0.0001),且在患者术后明显降低(P值均<0.05);三种miRNA的ROC AUC分别为0.851,0.848和0.739,三种miRNA组合在一起的AUC为0.873,均明显大于癌胚抗原;术后高表达miR-483-5p的患者较之低表这的生存期短(P=0.022)。结论血清miR-193a-3p,miR-337-5p和miR-483-5p可作为ESCC患者诊断或预后评估的潜在分子标志物。

Objective To investigate the expression level of serum miR-193a-3p,miR-337-5p and miR-483-5p in esophageal squamous cell carcinoma （ESCC） patients and to explore their value for diagnosis and prognosis of 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 and serum samples of 63 age- and sex- matched healthy individuals acted as the normal controls. TaqMan Low Density Assay was used to detect the deregulated miRNA in ESCC patients and then quanti- tative real-time PCR was used tO validate the upregulated miRNA miR-193a-3p,miR-337-5p and previously reported miR- 483-5p that was upregulated in oral squamous cell carcinoma（OSCC）. Finally, the three miRNA were evaluated for their clin- ical value in the diagnosis and predicting prognosis of ESCC. Results Compared with normal controls,serum levels of miR- 193a-3p,miR-337-Sp and miR-483-5p in ESCC patients were significantly up-regulated （0. 459±0. 339 vs 0. 195±0. 084 ,U =591±5. 686 ±5. 211 vs 2. 476±0. 808,U= 605; 32. 545±22. 479 vs 19. 509± 10. 601,U= 1 037, respectively, all P〈0. 0001） and their levels were significantly reduced after the surgical treatment （P〈0.05）. The areas under the ROC curve of serum miR-193a-3p,miR-337-5p,miR-483-5p, and miR-Panel were all larger than that of CEA. Univariate Kaplan-Meier a- nalysis revealed that ESCC patients with low expression level of miR-483-5p in postoperative serum exhibited higher survival rate than those with high level（P=0. 022）. Conclusion Serum miR-193a-3p,miR-337-5p and miR-483-Sp can be potential molecular biomarkers in the diagnosis and predicting prognosis of ESCC.