mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer

Giovanni Lanza¹ , Manuela Ferracin¹ , Roberta Gafà¹ , Angelo Veronese¹ , Riccardo Spizzo¹ , Flavia Pichiorri² , Chang-gong Liu² , George A Calin² , Carlo M Croce² and Massimo Negrini¹

¹Department of Experimental and Diagnostic Medicine and Interdepartment Center for Cancer Research, University of Ferrara, Ferrara, Italy

²Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA

author email corresponding author email

Molecular Cancer 2007, 6:54doi:10.1186/1476-4598-6-54


Published:	23 August 2007

Abstract

Background

Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome.

Results

We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response.

Conclusion

This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.