A serum microRNA signature for enhanced selection of people for lung cancer screening

Dear editor, Lung cancer (LC) is the leading cause of cancer-related mortality globally [1]. Earlier detection by screening can substantially reduce LC mortality [2, 3], but should be focused on those at highest risk [4]. Risk stratification for LC screening, which is mostly based on smoking history [5], is far from perfect [6]. Therefore, additional criteria to better define those at highest risk of LC are needed to enhance the efficiency and cost-effectiveness of LC screening. Besides risk prediction models incorporating classical LC risk factors [7], blood-based biomarkers such asmicroRNAs (miRNAs) have emerged as potential candidates to improve LC risk prediction [8].We aimed to derive and validate a blood-based miRNA signature predicting LC incidence in a large population-based cohort of older adults. A two-stage study design with a marker discovery and a marker validation phase was applied (Supplementary Materials and Methods). In the discovery phase, plasma samples from 20 LC cases and 20 LC-free controls (discovery set)were profiled using next-generation sequencing (NGS), and 20 differentially expressed miRNA candidates were identified (Supplementary Table S1, Supplementary Figures S1 and S2). Additional candidates were selected fromapreviously conducted literature reviewusing the following criteria: (1) miRNA evaluated in plasma or serum samples in Western populations; (2) miRNA included in a validated miRNA panel to discriminate LC cases from controls; (3) miRNA reported in ≥ 2 studies (Supplementary Table S2). In the marker validation phase, 40 miRNA candidates obtained through the NGS analyses and the lit-