Abstract 3061: Micro-RNA signature differences in lung cancer patients with ALK translocation, EGFR mutations and KRAS mutations.
Authors: Gasparini Pierluigi , Landi Lorenza , Carasi Stefania , Tibaldi Carmelo , Cascione Luciano , Alì Greta , D'Incecco Armida , Minuti Gabriele , Chella Antonio , Fontanini Gabriella , Cappuzzo Federico , Croce Carlo M. 
Published: August 2014

Background: Oncogenic driving mutations identify lung adenocarcinoma with different prognosis and sensitivity to targeted therapies. miRNAs are a new class of non-coding RNA involved in gene expression regulation and recent studies have suggested that miRNAs could be useful for stratifying lung cancer subtypes. How miRNAs are dysregulated in lung cancer patients with ALK translocation, EGFR or KRAS mutation is unknown. Aim of the present study is to identify miRNA signature differences according to the presence of specific oncogenic driver and correlation between miRNAs deregulation and drug response.

Materials and methods: The study was conducted in a cohort of 70 lung cancer patients including 68 primary cancer tissue (17 ALK positive tumors, 11 ALK negative EGFR positive tumors, 15 ALK negative KRAS positive tumors, 24 ALK negative EGFR and KRAS negative tumors defined as wild-type) with matched normal lung tissue (N=18) and 2 metastatic tissue. RNA was isolated from formalin-fixed paraffin-embedded tissue (FFPE), using the Recover ALL kit (Ambion). Data were processed according to manufacture guidelines. We used Limma to test for differential expression analysis of data. The miRNAs expression between tissues for all RT-qPCR was analyzed using the parametric t-test (unpaired, 2-tailed for validation).

Results: miRNA expression profile, cluster distinctly ALK+ patients from ALK- and normal lung tissue. Furthermore we found specific miRNAs subsets, within the ALK- group, able to sub-stratify KRAS versus EGFR careers and cluster sharply wild-type versus EGFR and wild-type versus KRAS as well. miRNAs belonging to the miR-515 family seems to be the most deregulated in the ALK+ vs ALK- comparison. Although their expression is stably high in normal tissues and ALK+ class they are highly downregulated in KRAS mutated versus EGFR mutated and versus ALK-/KRAS wild type/EGFR wild type (p-value &lt;0.001 for all comparisons).

Conclusions: miRNAs profile significantly differs in lung cancer patients with ALK translocation, EGFR mutations and KRAS mutations. Molecular analysis of the pathways involving the miR-515 family is ongoing in order to correlate their expression levels with patients’ outcome. Since miRNAs can induce resistance or sensitize to chemotherapies, in vitro modulation of miR-515 family expression level together with drugs test are ongoing in order to find better targeted therapies for ALK+ and ALK- patients.

Citation Format: Pierluigi Gasparini, Lorenza Landi, Stefania Carasi, Carmelo Tibaldi, Luciano Cascione, Greta Alì, Armida D'Incecco, Gabriele Minuti, Antonio Chella, Gabriella Fontanini, Federico Cappuzzo, Carlo M. Croce. Micro-RNA signature differences in lung cancer patients with ALK translocation, EGFR mutations and KRAS mutations. [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 3061. doi:10.1158/1538-7445.AM2013-3061

Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.