Abstract 1962: Differentially expressed microRNAs in adenocarcinomas of the lung and tumor-adjacent normal lung tissue.

Abstract

Abstract Introduction: Lung cancer is the most common cause of cancer deaths worldwide. The findings of new mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor and we need to know more about the genetic and epigenetic alterations in the tumors to better understand the biology of lung cancer. MicroRNAs are small non-coding RNAs that are involved in crucial biological processes in carcinogenesis by regulating gene expression at the post transcriptional level. In this project we have studied the microRNA expression patterns of lung adenocarcinomas and correspondent tumor-adjacent normal lung tissue and correlated the expression patterns with clinical data and mutational status. Methods: We have examined microRNA expression pattern in tumor tissues from 154 surgically resected lung adenocarcinomas and from 20 tumor-adjacent normal lung tissue samples. The expression of 1205 human microRNAs was conducted using the 60K microRNA microarray from Agilent technology. EGFR and KRAS mutation analyses were also performed. The analysis of differentially expressed microRNAs between groups of samples was done using significance analyses of microarrays (SAM) in the J-express software. We also performed survival analysis using univariate- and multivariate Cox regression analysis. The results are about to be validated by qRT-PCR. Results: Preliminary results show 129 differentially expressed microRNAs in tumor compared to the tumor-adjacent normal lung tissue. EGFR and KRAS mutations were found in 22/152 (14.5%) and 47/137 (34.3%) samples respectively. We have detected 17 microRNAs that are differentially expressed in EGFR mutated tumors compared to EGFR wildtype tumors. Two microRNAs were identified to have a strong association with time to progression in both univariate- and multivariate Cox regression analysis. Discussion: The microRNAs are thought to play an essential role in the development and progression of human malignancies, including lung cancer. We have identified several aberrantly expressed microRNAs that can discriminate lung adenocarcinoma tumor tissue from tumor-adjacent normal lung tissue samples. This can lead to the identification of biomarkers for early detection. 17 microRNAs were differentially expressed between EGFR mutated- and EGFR wt lung adenocarcinomas suggesting that microRNAs can be used as molecular biomarkers for lung cancer classification. We have also identified microRNAs that can be used as prognostic biomarkers. We are now confirming our results with qRT-PCR. We hypothesize that microRNA can be used as biomarkers for classification and clinical course. Citation Format: Maria Bjaanæs, Rita Halvorsen, Steinar Solberg, Lars Jørgensen, Odd-Terje Brustugun, Åslaug Helland. Differentially expressed microRNAs in adenocarcinomas of the lung and tumor-adjacent normal lung tissue. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1962. doi:10.1158/1538-7445.AM2013-1962