Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers.
Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers.
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DOI：
10.1186/1471-2407-11-374
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发表时间：
2011-08-24
期刊：
影响因子：
3.8
通讯作者：
Jiang F
中科院分区：
文献类型：
--
作者：
Shen J;Liu Z;Todd NW;Zhang H;Liao J;Yu L;Guarnera MA;Li R;Cai L;Zhan M;Jiang F
对 CT 发现的孤立性肺结节 (SPN) 进行明确的术前诊断一直是一项临床挑战。我们之前证明了 microRNA (miRNA) 可以用作肺癌诊断的生物标志物。在这里，我们研究血浆 microRNA 是否有助于在 CT 检测到 SPN 的个体中识别肺癌。通过使用定量逆转录酶 PCR 分析，我们首先确定了由 32 名恶性 SPN 患者、33 名良性 SPN 受试者和 29 名健康吸烟者组成的训练组中 5 种 miRNA 的血浆表达，以确定一组对肺癌具有高诊断效率的 miRNA。然后，我们在 76 名恶性 SPN 患者和 80 名良性 SPN 患者组成的测试组中验证了 miRNA 组。在训练集中，与良性 SPN 受试者和健康对照相比，恶性 SPN 患者中 miR-21 和 miR-210 显示出较高的血浆表达水平，而 miR-486-5p 的表达水平较低（所有 P ≤ 0.001）。在miR-21、miR-210和miR-486-5p的基础上建立了具有最佳预测的逻辑回归模型。组合使用的三种 miRNA 在区分肺部肿瘤和良性 SPN 时产生的受试者工作特征曲线下面积为 0.86，敏感性为 75.00%，特异性为 84.95%。测试集中 miRNA 组的验证证实了它们的诊断价值，比任何单个 miRNA 组都有显着的改进。血浆 miRNA 为 SPN 个体中肺癌的无创诊断提供了潜在的循环生物标志物，并且可以在临床试验中进一步评估。
Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs. By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs. In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one. The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.
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