肺腺癌microRNA的表达与预后的关系及其与厄洛替尼药效的相关性研究-外科学(胸外科)专业论文.docxVIP

万方数据 万方数据 Prognostic significance of microRNA expression in completely resected lung adenocarcinoma and the associated response to erlotinib Abstract Background: The mechanism of action of oncogenic or tumor suppressor microRNAs is not well understood. We examined the microRNA 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), miRNA microarrays were used to identify EGFR-related miRN As and their association with survival. In cohort 2 (107 patients with EGFR mutations), the miRN As and their association with survival and response to erlotinib were analyzed by qRT-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 miRNA-21 expression. Additionally, miRN 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 miRNA-21 (77.3% versus 41.7%, P0.01) and miRNA-145 (74.1% versus 42.6%, P0.01) expression is critical. The miRN A expression profiles differed significantly between patients with and without EGFR mutations. Conclusions: Lung adenocarcinoma patients with reduced miRNA-21 expression exhibit longer overall survival and a poor response rate to erlotinib. Increased miRN A-145 levels can predict overall survival, progression-free survival and excellent response rate to erlotinib. Postgraduate student：Guanzhong Yan（Th