Cancer Research Institute, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, Zhejiang, China.
Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China.
Proc Natl Acad Sci U S A. 2020 Oct 6;117(40):25036-25042. doi: 10.1073/pnas.2006212117. Epub 2020 Sep 17.
Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.
早期发现肺癌的微创检测以提高患者生存率是一项重大的未满足的临床需求。本研究旨在开发和验证一种血清多microRNA（multimiR）panel，作为一种微创检测方法，用于早期检测非小细胞肺癌（NSCLC），无论其吸烟状况、性别和种族如何。我们的研究包括 744 例 NSCLC 病例和 944 例匹配对照，包括吸烟者和不吸烟者、男性和女性，以及亚洲人和高加索人。使用 RT-qPCR 和严格控制的工作流程，我们在一个包含 180 例早期 NSCLC 病例和 216 例健康对照（男性吸烟者）的中国队列中定量了 520 种循环 microRNAs（miRNAs）的绝对表达。候选生物标志物在两个分别包含 432 例中国人和 218 例高加索人的病例对照队列中进行了验证（包括女性和不吸烟者）。使用两倍交叉验证开发了用于 NSCLC 检测的 multimiR 面板，并在包含 642 例受试者的另外三个亚洲队列中进行了验证。我们发现了 35 个候选 miRNA 生物标志物，验证了其中的 22 个，并开发了一个五miR 面板，在发现和验证队列中检测 NSCLC 的 AUC 为 0.936-0.984。该面板在三个独立的队列中得到了验证，AUC 分别为 0.973、0.916 和 0.917。在特异性为 90.7%时，五miR 检测对所有分期的敏感性为 81.3%，I 期和 II 期的敏感性为 82.9%，I 期 NSCLC 的敏感性为 83.0%。我们开发了一种微创的五miR 血清检测方法，用于检测早期 NSCLC，并在多个独立的患者队列中验证了其性能，无论其吸烟状况、性别和种族如何。
