Validation of a Serum 4-microRNA Signature for the Detection of Lung Cancer

Background: Our previous studies have identified a serum-based 4-microRNA signature that may help distinguish patients with lung cancer from non-cancer controls. Here, we used an extended independent cohort of 398 subjects to further validate the diagnostic ability of this 4-miRNA signature.   Methods: Using qRT-PCR, expression of the 4 miRNAs was assessed in a total of 398 sera that included 213 lung cancer patients (LCs) and 185 non-cancer controls (NCs). A logistic regression model using training-test sets, ROC curve analysis and t-test were used to test the impact of varying expression of these miRNAs on its diagnostic accuracy for lung cancer.   Findings: The levels of the 4 miRNAs were significantly higher in the serum of patients with LCs as compared to NCs. The expression of these 4 miRNAs did not vary with respect to patient's age, gender, smoking status, cancer histology, tumor stage, tumor size and lymph nodal metastasis. Using a logistic regression prediction model based on training and test sets analysis, we obtained the area under the curve of 0.921 (95% CI 0.876 - 0.966) on the test set with specificity 90.6%, sensitivity 77.9%, accuracy 84.1%, positive predictive value 89.8% and negative predictive value 79.5%.   Interpretation: We have verified that this serum 4-microRNA signature could provide a promising noninvasive biomarker for the prediction of lung cancer, particularly in patients with indeterminate lung nodules on screening CT scans.   Funding Statement: This work was supported by the National Institutes of Health (R21CA205414 to G.C.; R01CA154365 to D.G.B. and A.M.C.; U01CA157715 to D.G.B.); the University of Michigan Rogel Cancer Center Support Grant (P30 CA46592), the University of Michigan Rogel Cancer Center (G.C.), University of Michigan Department of Surgery Research Advisory Committee (G.C.) and generous patient and family donations to the Section of Thoracic Surgery, University of Michigan (G.C.). Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: Written consent was provided by all enrolled patients, and this study was approved by the University of Michigan Institutional and the VA Health System Review Board and Ethics Committee.