MicroRNA expression profiling of human metastatic cancers

Abstract

1059 Small non-coding microRNAs (miRNAs) contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. To test the hypothesis that a specific miRNA expression signature characterizes the metastatic phenotype of solid tumors, we performed miRNA micro-array analysis on 43 paired primary tumors and lymphnode metastasis. Specimens were collected at the Department of Pathology, Thomas Jefferson University from 43 patients consisting in 13 breast carcinomas, 10 lung cancers, 10 bladder urothelial cell carcinomas and 10 colon cancers. 5 μg of total RNA from each sample were used. Hybridization of biotin-labeled complementary DNA was performed on a two new miRNA microarray chip (OSU_CCC version 3.0 and 4.0), which contains ∼1,100 miRNA probes (326 human and 249 mouse miRNA genes, spotted in duplicates). We identified a common metastatic cancer miRNA signature mainly composed by over-expressed miRNAs. Some of these miRNAs (miR-10b, miR-20a, miR-21) have a well characterized association with cancer progression. In particular, in metastatic breast cancers there was an up-regulation of miR-450a, miR-148a and a down-regulation of miR- 205, miR-130b. In metastatic lung cancer there was an up-regulation of miR-369–3p and a down-regulation of miR-138–1. In metastatic bladder cancer there was an up-regulation of miR-29a, miR-10b, miR-126 and a down-regulation of miR-145, miR-143, and in metastatic colon cancer there was an up-regulation of miR-138, miR-21 and a down-regulation of miR-20a and miR-204. Moreover, in the metastatic samples we found that miRNAs associated to inflammation and immune response were over-expressed due to the partial contamination of our samples by the lymphocytes. The over-expression of most miRNAs that we found over-expressed in the primary tumors had been previously reported in published signatures of the corresponding normal tissues, thus confirming that miRNA signatures are a potent tool in classifying tissues of different origin.Our results indicate that specific miRNAs may be directly involved in cancer metastasis and that they may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets. No significant financial relationships to disclose.