Role of plasma MicroRNAs in the early diagnosis of non-small-cell lung cancers: a case-control study

Background: Lung cancer is a leading cause of cancer death worldwide. Early diagnosis is essential for improvements of prognosis and survival of the patients. Altered expressions in many cancer types including lung cancer and stable existence in plasma make microRNAs (miRNAs) a group of potentially useful biomarkers for clinical assessments of patients with lung cancer. In this study, we evaluate the potential values of miRNAs as plasma biomarkers for early diagnosis in non-small-cell lung cancers (NSCLC) by comparing with other typical plasma biomarkers. Methods: We analyzed the clinical and laboratory characteristics of 59 early-staged NSCLC (I-IIIA) patients and non-cancer controls by 1: 1 matching age and gender from January 2012 to February 2014 in Xuanwu Hospital, Beijing, China. Peripheral blood samples from patients and controls before surgery were collected, and plasma was separated. Expression of ten miRNAs in the plasma of the patients and controls was detected by quantitative real-time polymerase chain reaction. Other typical markers, such as SCC, CEA, and CYFRA21-1 in plasma were also detected. The early diagnostic ability of miRNAs and other markers were evaluated by receiver-operating-characteristic (ROC) curve analysis. The sensitivity, specificity, and area under the curve were calculated for the cut-off value. Results: Plasma CYFRA21-1, miRNA-486 and miRNA-210 levels were significantly different in patients with NSCLC than those in controls (CYFRA21-1: 8.896 +/- 7.681 vs. 5.892 +/- 6.028, P=0.020; miR-486: 2.778 +/- 0.778 vs. 1.746 +/- 0.892, P<0.001; miR-210: 4.836 +/- 3.374 vs. 2.829 +/- 2.503, P<0.001). Area under ROC curve of CYFRA21-1, miR-486 and miR-210 were 0.624 (sensitivity: 0.576, specificity: 0.797), 0.848 (sensitivity: 0.831, specificity: 0.780) and 0.751 (sensitivity: 0.746, specificity: 0.746), respectively. The optimal cut-off value of CYFRA21-1, miRNA-486 and miRNA-210 were 6.595, 1.988 and 3.341, respectively to discriminate patients from controls. Plasma markers combined diagnosis ability had the highest sensitivity: 0.983, but the specificity was low. miR-486, miR-210 and CYFRA21-1 combined diagnosis ability was the highest, and the AUC was 0.924 (sensitivity: 0.847; specificity: 0.728). Conclusions: The results suggest that miRNA-486 and miR-210 could be potential blood-based biomarkers for early diagnosis of NSCLC. miRNAs and other lab indexes may be combined to early diagnose NSCLC, which showed better ability of screening patients.