A plasma miRNA signature for lung cancer early detection

Abstract

The early detection of lung cancer continues to be a major clinical challenge. Using whole-transcriptome next-generation sequencing to analyze lung tumor and the matched noncancerous tissues, we previously identified 54 lung cancer-associated microRNAs (miRNAs). The objective of this study was to investigate whether the miRNAs could be used as plasma biomarkers for lung cancer. We determined expressions of the lung tumor-miRNAs in plasma of a development cohort of 180 subjects by using reverse transcription PCR to develop biomarkers. The development cohort included 92 lung cancer patients and 88 cancer-free smokers. We validated the biomarkers in a validation cohort of 64 individuals comprising 34 lung cancer patients and 30 cancer-free smokers. Of the 54 miRNAs, 30 displayed a significant different expression level in plasma of the lung cancer patients vs. cancer-free controls (all P < 0.05). A plasma miRNA signature (miRs-126, 145, 210, and 205-5p) with the best prediction was developed, producing 91.5% sensitivity and 96.2% specificity for lung cancer detection. Diagnostic performance of the plasma miRNA signature had no association with stage and histological type of lung tumor, and patients’ age, sex, and ethnicity (all p > 0.05). The plasma miRNA signature was reproducibly confirmed in the validation cohort. The plasma miRNA signature may provide a blood-based assay for diagnosing lung cancer at the early stage, and thereby reduce the associated mortality and cost.