Abstract 4139: Clinical evaluation of microRNA expression profiling in non-small cell lung cancer

CONTEXT: MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level. miRNAs play an important role in tumorigenesis since they have functions similar to oncogene or tumor suppressors and represent a new class of powerful tools for cancer prevention and therapeutics. Especially circulating miRNAs in plasma seem to be very promising novel tumor biomarkers, since their expression is correlated to diagnosis, prognosis and prediction of response to treatment. OBJECTIVE: The aim of our study was to evaluate mature miRNAs as novel tumor biomarkers in NSCLC, by exploring global expression profile of miRNAs in NSCLC paired fresh tissues and corresponding plasma samples. METHODS: FlexmiR bead array (Luminex) assay was utilized for miRNA expression profiling in 21 surgically removed NSCLC fresh tissues and their corresponding adjacent non-cancerous tissues. According to our FlexmiR results, evaluated by three different statistical approaches, 23 miRNAs were found to be differentially expressed. Our FlexmiR experiments were validated for four of these microRNAs in 40 paired NSCLC and matched corresponding adjacent non-cancerous tissues by Taqman RT-qPCR microRNA assays (Applied Biosystems). Moreover, total RNA was extracted from 37 corresponding plasma samples and miR-21 expression was quantitated by RT-qPCR. RESULTS: 23 miRNAs were found to be differentially expressed in NSCLC by the FlexmiR assay. Four of these, miR-21, miR-126*, miR-30d and miR-451, were further evaluated by quantitative RT-qPCR. The expression level of miR-21 was significantly higher in NSCLC tissues than in adjacent normal tissues (P=0.002); while miR-126* (P=0.000), miR-30d (P=0.000) and miR-451 (P=0.000) were down-regulated in NSCLC. Interestingly, high miR-21 expression and low miR-126* and miR-30d expression were associated with disease free survival (P=0.027, P= 0.047 and P=0.048 respectively). Levels of circulating miR-21 in plasma of NSCLC patients were significantly higher in NSCLC than in healthy volunteers (P=0.003). Circulating miR-21 in plasma was found to be an independent prognostic factor for NSCLC (P=0.019). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4139. doi:1538-7445.AM2012-4139