MicroRNA Expression Profiling of Sputum for the Detection of Early and Locally Advanced Non-Small-Cell Lung Cancer: A Prospective Case–Control Study

Abstract

Background: Non-small-cell lung cancer (NSCLC) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. MicroRNAS (miRNAS) are a class of short, noncoding RNA molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting NSCLC. We investigated the stage-specific NSCLC detection potential of an efficient panel of 3 miRNAS (MIR-21, MIR-210, MIR-372) using a single sputum sample. Methods: A single spontaneously expectorated sputum sample was prospectively collected from 21 early NSCLC (≤stage II) patients, 22 advanced NSCLC (≥stage III) patients, and 10 control subjects. MiRNA expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. Results: Mean tumour size (±95% confidence interval) in the early and advanced NSCLC patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced NSCLC cases respectively. In comparing the early NSCLC group with the control group, the miRNA panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced NSCLC group, the miRNA panel detected NSCLC with a sensitivity and specificity of 64% and 100% respectively. Conclusions: A sputum MIR-21, MIR-210, and MIR-372 expression profile might provide a sensitive and highly specific means for detecting NSCLC. Sputum miRNA analysis demonstrates promise as a potential complementary screening tool.