Contributions of Circulating microRNAs for Early Detection of Lung Cancer

SIMPLE SUMMARY: Blood-based cancer biomarkers are a minimally invasive means to achieve improved assessment of risk and/or earlier detection of lung cancer. Using serum samples from individuals that went on to develop lung cancer within one year following blood draw and from matched controls, we investigated 30 microRNAs for individual and combined utility to discriminate lung cancer cases from controls. We additionally assessed the contributions of top-performing microRNA candidates for improving on the performance of a previously validated four-protein marker panel for lung cancer detection. The results of this study indicate complementary performance of combining circulating microRNA and the four-protein-marker panel in assays for early detection of lung cancer. ABSTRACT: There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) consisting of the precursor form of surfactant protein B (Pro-SFTPB), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA21-1) was additionally assessed. Of the 30 miRNAs evaluated, five (miR-320a-3p, miR-210-3p, miR-92a-3p, miR-21-5p, and miR-140-3p) were statistically significantly (Wilcoxon rank sum test p < 0.05) elevated in case sera compared to controls, with individual AUCs ranging from 0.57–0.62. Compared to the 4MP alone, the combination of 3-miRNAs + 4MP improved sensitivity at 95% specificity by 19.1% ((95% CI of difference 0.0–28.6); two-sided p: 0.006). Our findings demonstrate utility for miRNAs for early detection of lung cancer in combination with a four-protein marker panel.