Xing Lingxiao, Su Jian, Guarnera Maria A, Zhang Howard, Cai Ling, Zhou Rixin, Stass Sanford A, Jiang Feng
Department of Pathology, Hebei Medical University, Shijiazhuang, China.
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
Clin Cancer Res. 2015 Jan 15;21(2):484-9. doi: 10.1158/1078-0432.CCR-14-1873.
The early detection of lung cancer in heavy smokers by low-dose CT (LDCT) can reduce the mortality. However, LDCT screening increases the number of indeterminate solitary pulmonary nodules (SPN) in asymptomatic individuals, leading to overdiagnosis. Making a definitive preoperative diagnosis of malignant SPNs has been a clinical challenge. We have demonstrated that sputum miRNAs could provide potential biomarkers for lung cancer. Here, we aimed to develop sputum miRNA biomarkers for diagnosis of malignant SPNs.
Using quantitative RT-PCR, we evaluated expressions of 13 sputum miRNAs, previously identified sputum miRNA signatures of lung cancer, in a training set of 122 patients with either malignant (n = 60) or benign SPNs (n = 62) to define a panel of biomarkers. We then validated the biomarker panel in an internal testing set of 136 patients with either malignant (n = 67) or benign SPNs (n = 69), and an external testing cohort of 155 patients with either malignant (n = 76) or benign SPNs (n = 79).
In the training set, a panel of three miRNA biomarkers (miRs21, 31, and 210) was developed, producing 82.93% sensitivity and 87.84% specificity for identifying malignant SPNs. The sensitivity and specificity of the biomarkers in the two independent testing cohorts were 82.09% and 88.41%, 80.52% and 86.08%, respectively, confirming the diagnostic value.
Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective study in a large population to validate the biomarkers is needed.
低剂量CT（LDCT）用于重度吸烟者肺癌的早期检测可降低死亡率。然而，LDCT筛查增加了无症状个体中不确定的孤立性肺结节（SPN）数量，导致过度诊断。对恶性SPN进行明确的术前诊断一直是一项临床挑战。我们已经证明痰液miRNA可为肺癌提供潜在的生物标志物。在此，我们旨在开发用于诊断恶性SPN的痰液miRNA生物标志物。
我们使用定量逆转录聚合酶链反应（RT-PCR），在一个由122例患有恶性（n = 60）或良性SPN（n = 62）的患者组成的训练组中，评估了13种先前已确定的肺癌痰液miRNA特征的痰液miRNA的表达，以确定一组生物标志物。然后，我们在一个由136例患有恶性（n = 67）或良性SPN（n = 69）的患者组成的内部测试组以及一个由155例患有恶性（n = 76）或良性SPN（n = 79）的患者组成的外部测试队列中验证了该生物标志物组。
在训练组中，开发了一组由三种miRNA生物标志物（miR-21、miR-31和miR-210）组成的标志物，用于识别恶性SPN的灵敏度为82.93%，特异性为87.84%。在两个独立测试队列中，这些生物标志物的灵敏度和特异性分别为82.09%和88.41%、80.52%和86.08%，证实了其诊断价值。
痰液miRNA生物标志物可通过术前诊断恶性SPN来改善重度吸烟者肺癌的LDCT筛查。然而，需要在大量人群中进行前瞻性研究以验证这些生物标志物。
