Altered microRNA Expression in Adenocarcinoma of Lung from Smokers and Never-Smokers.
Ming Guo, Min Huang, George A Calin, Kenneth R Hess, Wei Zhang. The University of Texas M.D. Anderson Cancer Center, Houston; Fox Chase Cancer Center, Philadelphia, PA
Background: Recent studies on the altered microRNA (miRNA) expression in lung cancer have shed light on our understanding in lung cancer carcinogenesis at epigenetic level. Identifying altered miRNA expression that is independent of tobacco smoking in lung cancer may enhance our understanding further on the epigenetic events in lung cancer that may lead to the development of new tests for early detection, prognosis and assessment for treatment response in lung cancer patients. In this study, we conducted miRNA profiling analysis using microarray assay in lung adenocarcinoma from smokers and non-smokers.
Design: From the tumor bank at Fox Chase Cancer Center, we collected 50 lung adenocarcinomas with matched non-neoplastic lung tissue. In the cohort, 25 patients had no history of tobacco smoking. MiRNA expression profiling analysis was conducted using Human miRNA V2 Oligo Microarray Kit (Agilent Technologies, Alto, CA). Feature Extraction (188.8.131.52) software was used to link a feature to a design file and determine the relative fluorescence intensity of each sample. The validation tests were conducted using miRT-PCR assay (Applied Biosystems, Foster City, CA). The altered miRNA expression in lung adenocarcinoma was compared between smokers and non-smokers.
Results: In smokers, we identified 23 abnormally expressed miRNAs with 8 up-regulated and 15 down-regulated. In non-smokers, 26 miRNAs were found abnormally expressed with 8 up-regulated and 18 down-regulated. MiR-21, mir-196a and miR-310b were exclusively up-regulated in non-smokers, while miR-130a, miR-140-3p, miR-144a, miR-187* and miR-497 were exclusively down-regulated in smokers. Among the up-regulated miRNAs, mir-130b, mir-210, mir-503 and mir-21* were expressed in both smokers and never smokers. In down-regulated, miRNAs, miR-126*, miR-126, Mir-133b, miR-139-5p, miR-145*, miR-145, miR-218, miR-30*, miR-30a, miR-338-3p, miR-451, miR-468-5p and miR551b were expressed in both smokers and non-smokers. The altered expression of miR-310b, miR139-5p and miR486-5p were confirmed using real time RT-PCR.
Conclusions: The finding of miRNAs abnormally expressed in both smokers and non-smokers suggested that the altered miRNA expression that is independent of tobacco smoking may represent an epigenetic predisposition in carcinogenesis of lung adenocarcinoma.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Monday, February 28, 2011 1:00 PM
Poster Session II # 249, Monday Afternoon