Prognostic Significance Of MicroRNA Expression In Completely Resected Lung Adenocarcinoma And The Associated Response To Erlotinib

Background: The mechanism of action of oncogenic or tumor suppressor micro RNAs is not well understood. We examined the micro RNA expression profile in completely resected lung adenocarcinoma and examined the associated response to erlotinib.Methods: The lung adenocarcinoma tissue and adjacent normal lung parenchyma of 226 stage IIB and IIIA patients who underwent complete resection were obtained for 2 separate retrospective cohorts. In cohort 1(119 patients; 80 with EGFR mutations and 39 without), mi RNA microarrays were used to identify EGFR-related mi RN As and their association with survival. In cohort 2(107 patients with EGFR mutations), the mi RN As and their association with survival and response to erlotinib were analyzed by q RT-PCR. Cox proportional hazards regression was used to evaluate the effect of treatment on survival.Results: Erlotinib is associated with a significant improvement in overall survival(P=0.0075, cohort 1; P=0.0372, cohort 2) and disease progression(P=0.6929, cohort 1; P=0.3347, cohort 2) in patients with reduced mi RNA-21 expression. Additionally, mi RN A-145 is strongly associated with overall survival(P=0.0008, cohort 1; P=0.0131, cohort 2) and progression- free survival(P=0.0198, cohort 1; P=0.0269, cohort 2). Understanding the response rate to erlotinib relative to mi RNA-21(77.3% versus 41.7%, P<0.01) and mi RNA-145(74.1% versus 42.6%, P<0.01) expression is critical. The mi RN A expression profiles differed significantly between patients with and without EGFR mutations.Conclusions: Lung adenocarcinoma patients with reduced mi RNA-21 expression exhibit longer overall survival and a poor response rate to erlotinib. Increased mi RN A-145 levels can predict overall survival, progression-free survival and excel ent response rate to erlotinib.