Department of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cancer Prev Res (Phila). 2010 Dec;3(12):1571-8. doi: 10.1158/1940-6207.CAPR-10-0128. Epub 2010 Sep 23.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. We previously identified genetic signatures whose genomic copy number aberrations were associated with early stage NSCLC. Here, we aimed to develop a panel of genes that could be detected in sputum for NSCLC early detection. We first optimized a panel of genes by using an in situ minichip for measuring changes of the signatures in sputum of a case-control cohort of 49 NSCLC patients, 49 patients with chronic obstructive pulmonary disease (COPD), and 49 healthy smokers. We then validated the genes in an independent cohort of 69 NSCLC patients and 65 noncancer subjects. The results were compared with those of sputum cytology. Fifteen genes showed significant differences of their copy number changes in sputum between NSCLC and both COPD and healthy subjects. A logistic regression model with the best prediction was built on the basis of 6 genes, ENO1, FHIT, HYAL2, SKP2, p16, and 14-3-3zeta. The composite of the 6 genes produced 86.7% sensitivity and 93.9% specificity in distinguishing stage I NSCLC patients from the noncancer individuals. Furthermore, the genes had higher sensitivity (86.9%) in identification of squamous cell carcinoma (SCC) than in adenocarcinoma of the lungs (80.8%; P < 0.05). Validation of the genes in the independent cohort confirmed their diagnostic power that also showed higher accuracy for lung SCCs than for sputum cytology. The gene panel could provide sputum-based markers that have the potential to improve early detection of lung SCCs.
非小细胞肺癌（NSCLC）是癌症死亡的主要原因。早期发现 NSCLC 可以改善其预后。我们之前确定了一些遗传特征，其基因组拷贝数异常与早期 NSCLC 相关。在这里，我们旨在开发一种可在痰液中检测 NSCLC 的基因组合。我们首先使用原位微芯片优化了一组基因，用于测量 49 例 NSCLC 患者、49 例慢性阻塞性肺疾病（COPD）患者和 49 例健康吸烟者的痰液中特征的变化。然后，我们在 69 例 NSCLC 患者和 65 例非癌症患者的独立队列中验证了这些基因。结果与痰液细胞学结果进行了比较。15 个基因在 NSCLC 与 COPD 和健康对照者的痰液中其拷贝数变化有显著差异。基于 6 个基因（ENO1、FHIT、HYAL2、SKP2、p16 和 14-3-3zeta）建立了最佳预测的逻辑回归模型。6 个基因的组合在区分 I 期 NSCLC 患者和非癌症个体方面产生了 86.7%的敏感性和 93.9%的特异性。此外，这些基因在识别鳞状细胞癌（SCC）方面比在肺腺癌（80.8%）具有更高的敏感性（P < 0.05）。在独立队列中验证这些基因证实了它们的诊断能力，这也表明基因组合比痰液细胞学具有更高的 SCC 准确性。该基因组合可以提供基于痰液的标志物，具有提高 SCC 早期检测的潜力。
