Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
Departments of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Cancer Biomark. 2019;26(2):219-227. doi: 10.3233/CBM-190161.
Analysis of molecular changes in sputum may help diagnose lung cancer. Long non-coding RNAs (lncRNAs) play vital roles in various biological processes, and their dysregulations contribute to the development and progression of lung tumorigenesis. Herein, we determine whether aberrant lncRNAs could be used as potential sputum biomarkers for lung cancer.
Using reverse transcription PCR, we measure expressions of lung cancer-associated lncRNAs in sputum of a discovery cohort of 67 lung cancer patients and 65 cancer-free smokers with benign diseases and a validation cohort of 59 lung cancer patients and 60 cancer-free smokers with benign diseases.
In the discovery cohort, four of the lncRNAs displayed a significantly different level in sputum of lung cancer patients vs.cancer-free smokers with benign diseases (all P< 0.001). From the four lncRNAs, three lncRNAs (SNHG1, H19, and HOTAIR) are identified as a biomarker panel, producing 82.09% sensitivity and 89.23% specificity for diagnosis of lung cancer. Furthermore, the biomarker panel has a higher sensitivity (82.09% vs. 52.24%, P= 0.02) and a similar specificity compared with sputum cytology (89.23% vs. 90.77%, P= 0.45). In addition, the lncRNA biomarker panel had a higher sensitivity (87.50% vs. 70.07%, p= 0.03) for diagnosis of squamous cell carcinoma compared with adenocarcinoma of the lung, while maintaining the same specificity (89.23%). The potential of the sputum lncRNA biomarkers for lung cancer detection is confirmed in the validation cohort.
We have for the first time shown that the analysis of lncRNAs in sputum might be a noninvasive approach for diagnosis of lung cancer.
分析痰液中的分子变化可能有助于诊断肺癌。长链非编码 RNA（lncRNA）在各种生物过程中发挥着重要作用，其失调导致肺癌的发生和发展。在此，我们确定异常的 lncRNA 是否可以作为潜在的肺癌痰液生物标志物。
我们使用逆转录 PCR 测量了 67 例肺癌患者和 65 例患有良性疾病的无癌吸烟者的痰液中与肺癌相关的 lncRNA 的表达情况，并在一个验证队列中测量了 59 例肺癌患者和 60 例患有良性疾病的无癌吸烟者的痰液中的表达情况。
在发现队列中，有 4 个 lncRNA 在肺癌患者的痰液中与无癌吸烟者的痰液相比显示出明显不同的水平（均 P<0.001）。从这四个 lncRNA 中，三个 lncRNA（SNHG1、H19 和 HOTAIR）被确定为一个生物标志物组合，用于诊断肺癌的敏感性为 82.09%，特异性为 89.23%。此外，与痰液细胞学相比，该生物标志物组合具有更高的敏感性（82.09% vs. 52.24%，P=0.02）和相似的特异性（89.23% vs. 90.77%，P=0.45）。此外，与肺腺癌相比，该 lncRNA 生物标志物组合对鳞状细胞癌的诊断具有更高的敏感性（87.50% vs. 70.07%，p=0.03），而特异性保持不变（89.23%）。该痰液 lncRNA 生物标志物用于肺癌检测的潜力在验证队列中得到了证实。
我们首次表明，分析痰液中的 lncRNA 可能是诊断肺癌的一种非侵入性方法。
