Serum miR-499 as a novel diagnostic and prognostic biomarker in non-small cell lung cancer.

The aim of the present study was to determine whether serum miR-499 may be used as a biomarker for early detection of non-small cell lung cancer (NSCLC). The present study was designed as an initial screening phase and a subsequent validation phase. In the screening phase, we analyzed serum levels of miR-499 in a subset of 40 patients with stage I (n=20) and stage IV (n=20) NSCLC. In the validation phase, miR-499 expression levels in serum (n=514) and tissue (n=136) from NSCLC patients were detected in a large and independent cohort of 514 patients. miR-499 in the screening phase was found to be significantly elevated in the serum of stage I NSCLC patients compared with that in stage IV NSCLC patients (P<0.001). Validation analysis showed that serum miR-499 levels were robust in differentiating NSCLC patients from control subjects [area under the curve (AUC)=0.906; 95% confidence interval (CI)=0.879 to 0.929). Serum miR-499 levels were significantly lower in stage III and IV patients compared with those with stage I (both P<0.001) or II (both P<0.001). Low serum miR-499 levels were associated with shorter overall survival and served as an independent prognostic biomarker in NSCLC patients [hazard ratio (HR)=1.63; 95% CI=1.33-2.0; P<0.0001). In addition, low serum levels of miR-499 indicated a poor disease-free survival in stage I-II NSCLC patients. Serum miR-499 may prove to be a promising biomarker for early detection and prognosis prediction of NSCLC.