Circulating MicroRNAs in Relation to EGFR Status and Survival of Lung Adenocarcinoma in Female Non-Smokers

Objectives: Lung adenocarcinoma is considered a unique disease for Asian female non-smokers. We investigated whether plasma microRNA (miRNA) expression profiles are different by the EGFR status and are associated with survival outcomes of the patients. Methods: Using real-time RT-PCR, we analyzed the expression of 20 miRNAs in the plasma of 105 female patients with lung adenocarcinoma. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to determine the association between miRNA expression and overall survival. Time dependent receiver operating characteristic (ROC) analysis was also performed. Results: In the 20 miRNAs, miR-122 were found differently expressed between wild and mutant EGFR carriers (P=0.018). Advanced disease stage and tumor metastasis were independently associated with poor prognosis of patients with lung adenocarcinoma (P=0.010 and 1.0x10(-4)). Plasma levels of miR-195 and miR-122 expression were also associated with overall survival in the patients, especially in those with advanced stage (HR=0.23, 95% CI: 0.07-0.84; and HR=0.22, 95% CI: 0.06-0.77) and EGFR mutation (HR=0.27, 95% CI: 0.08-0.96; and HR=0.23, 95% CI=0.06-0.81). Moreover, a model including miR-195, miR-122 may predict survival outcomes of female patients with lung adenocarcinoma (AUC=0.707). Conclusions: Circulating miR-195 and miR-122 may have prognostic values in predicting the overall survival as well as predicting EGFR mutation status in non-smoking female patients with lung adenocarcinoma. Measuring plasma levels of miR-195 and miR-122 may especially be useful in EGFR mutant patients with lung adenocarcinoma.