Integrating DNA methylation and microRNA biomarkers in sputum for lung cancer detection.

BACKGROUND

Abnormal microRNA (miRNA) expressions and promoter methylation of genes detected in sputum may provide biomarkers for non-small lung cancer (NSCLC). Here, we evaluate the individual and combined analysis of the two classes of sputum molecular biomarkers for NSCLC detection.

RESULTS

We analyze expression of 3 miRNAs (miR-21, miR-31, and miR-210) and methylation of 3 genes (, , and ), which were previously identified as potential biomarkers for NSCLC, in sputum of a set of 117 stage I NSCLC patients and 174 cancer-free smokers. The results are validated in a different set of 144 stage I NSCLC patients and 171 controls. The panel of 3 miRNA biomarkers has 81.5 % sensitivity and 85.9 % specificity; the panel of 3 methylation biomarkers displays 82.9 % sensitivity and 76.4 % specificity for NSCLC detection. Integrated analysis of 2 miRNAs (miR-31 and miR-210) and 2 genes ( and ) yields higher sensitivity (87.3 %) and specificity (90.3 %) compared with the individual panels of the biomarkers ( < 0.05). Combined analysis of all the 3 miRNAs and 3 genes does not have performance superior to that of the panel of 2 miRNAs and 2 genes ( > 0.05). The performance of combined use of the two classes of biomarkers was confirmed in the validation set.

CONCLUSIONS

The integration of two different classes of biomarkers synergistically improves both the sensitivity and the specificity for the early detection of NSCLC.