血浆miRNA-20a和miRNA-210对肺癌的诊断价值评价

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摘要目的: 探讨血浆miRNA20a和miRNA210表达水平用于肺癌诊断的可行性及临床价值。方法: 采用荧光定量PCR法检测58例肺癌患者和46例良性肺疾病患者血浆miRNA20a和miRNA210的表达。同时分析血浆miRNA20a和miRNA210表达水平与患者临床病理特征的相关性。构建受试者工作特征（ROC）曲线，评估这两类miRNA诊断肺癌的效能。根据ROC曲线确定这两类血浆miRNAs诊断肺癌的折点（临界值），计算敏感性、特异性等，并与经典的肿瘤标志物癌胚抗原、细胞角蛋白19（Cyfra211）的测定结果进行比较。结果：肺癌患者血浆中miRNA20a和miRNA210的表达水平均明显高于良性肺疾病对照组（P<0.01）。血浆miRNA20a的表达与患者的临床病理特征无相关性，而血浆miRNA210表达水平与肺癌的组织学类型、分化程度及临床分期显著相关（P=0.008、P=0.041和P=0.016）。血浆miRNA20a和miRNA210的ROC曲线下面积（AUC）分别为0.883（95%可信区间0.821～0.946）和0.824（95%可信区间0.745～0.904），高于癌胚抗原和Cyfra211的0.656（95%可信区间0.551～0.761）和0.754（95%可信区间0.658～0.847）。血浆miRNA20a和miRNA210诊断肺癌的敏感性(77.6%和75.9%)和准确性(81.7%和77.9%)高于癌胚抗原(44.8%和62.5%)和Cyfra211(56.9%和72.1%)，这两种miRANs联合检测能进一步提高肺癌诊断的敏感性，但特异性略有下降。此外，两种miRANs联合癌胚抗原或Cyfra211能进一步提高对肺癌的诊断效能。结论：血浆miRNA20a和miRNA210有可能作为诊断肺癌的生物标志物。

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关键词 ：荧光定量PCR, 肺癌, miRNA-20a, miRNA-210, 诊断

Abstract：Objective: To evaluate the diagnostic values of plasma miRNA20a and miRNA210 expression for lung cancer. Methods: The expression levels of plasma miRNA20a and miRNA210 were determined by fluorescence quantitative PCR in 58 lung cancer patients and 46 benign lung disease patients(cancerfree controls). The correlations between the two miRNAs levels in plasma and clinicopathological characteristics of patients with lung cancer were analyzed. The diagnostic performance of each miRNA to distinguish lung cancer from benign lung disease was evaluated using the receiver operating characteristic(ROC) curve analysis. According to the optimal cutoff point chosen by ROC curve analysis, sensitivity, specificity, positive value(PPV), negative predictive value (NPV) and accuracy were calculated. The diagnostic value of the two miRNAs for lung cancer was compared with tumor markers carcinoembryonic antigen(CEA) and Cyfra211. Results: The levels of plasma miRNA20a and miRNA210 in lung cancer patients were significantly elevated than those in benign lung disease patients (P<0.01). No significant correlation was found between plasma miRNA20a levels and clinicopathological characteristics of lung cancer patients, whereas the expression levels of plasma miRNA210 was significantly correlated with tumor histological types, differential degree and clinical stages(P=0.008, P=0.041 and P=0.016). The area under ROC curve of the two miRNAs were 0.883（95%CI, 0.821-0.946）and 0.824（95%CI, 0.745-0.904）, which were higher than those of CEA (0.656, 95%CI, 0.551-0.761) and Cyfra211(0.754, 95%CI, 0.658-0.847), respectively. The sensitivity(77.6% and 75.9%) and accuracy(81.7% and 77.9%) of plasma miRNA20a and miRNA210 for diagnosing lung cancer were higher than those of CEA(44.8% and 62.5%) and Cyfra211(56.9% and 72.1%). And the sensitivity was increased with miRNA20a in combination with miRNA210. Moreover, the combination of plasma miRNA20a and miRNA210 with CEA or Cyfra211 further raised the sensitivity in diagnosis of lung cancer, despite slightly decreased specificity. Conclusion: Plasma miRNA20a and miRNA210 may be used as promising biomarkers in the diagnosis of lung cancer.

收稿日期: 2016-12-20

通讯作者: 李坚（通讯作者），教授，主任医师，博士生导师，E-mail: lijian541226@163.com

作者简介: 夏贤斌（1989—），男，硕士研究生

引用本文:

夏贤斌1，李坚1，汪毅2. 血浆miRNA-20a和miRNA-210对肺癌的诊断价值评价[J]. 江苏大学学报:医学版, 2017, 27(01): 47-52. XIA Xian-bin1, LI Jian1, WANG Yi2. Evaluation of clinical value of plasma miRNA-20a and miRNA-210 in diagnosis of lung cancer. Journal of Jiangsu University(Medicine Edition), 2017, 27(01): 47-52.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2017/V27/I01/47

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