Abstract 442: Increased miR-let7c level indicates transition from localized bladder cancer to metastasis

Abstract

Abstract Purpose/Objective(s): MicorRNAs are a group of short ribonucleic acid molecules with an average of 22 nucleotides and play an important role in regulation of gene expression. Because the microRNA profiles of tumor are related to cancer development and prognostication, it becomes a new frontier of cancer research. The current tools for studying microRNA like microarray have limited dynamic range and poor sensitivity, and Taqman microRNA assay has higher sensitivity but limited number of microRNAs. The SOLiD system provides a sensitive and robust assay for discovery and profiling of novel microRNAs using sequencing by ligation. The aim of this study is to find key miRNA which can provide insights into the cancer cell invasion and metastasis. Materials/Methods: 12 bladder cancer FFPE samples were used in this study, including 6 cases of stage N0, 3 cases of stage N1 and 3 cases of stage N2. Total RNA from FFPE blocks was isolated by Ambion RecoverAll Total Nucleic Acid Isolation kit according to manufacturer's instructions. The concentration and quality of total RNA were examined by Nanodrop 1000 spectrophotometer. The small RNA was enriched by flashPAGE fractionation and the microRNA library was built using Ambion SOLiD Small RNA Expression Kit with the barcode system (Life Technologies, CA, US). 35 bp long reads were generated on the SOLiD (version 3.0) sequencing system (Life Technologies) and were analyzed by using the SOLiD System Small RNA Analysis Tool (Life Technologies). Results: Analyzed samples were from male caucasian patients with a median age of 63.5 years. Tumors were all grade 3 urothelial carcinomas. Patients had T1-4 and M0-1 disease. We examined global miRNA expression in bladder cancer FFPE samples, and SOLiD results revealed that the expression of 10 microRNAs significantly differed between N0 stage and N1/2 stage. miR-let7c precursor and mature miR-let7c were upregulated in samples from patients with lymphnode metastasis. A previous study from Leite et al. showed that miR-let7c expression was similar in matched FFPE and frozen prostate cancer tissue with a Pearson's correlation coefficient of 0.927. Conclusion: miR-let7c expression is associated with the presence of lymphnode metastasis in high-grade urothelial bladder cancer. 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 442. doi:1538-7445.AM2012-442