This article is a US Government work and, as such, is in the public domain in the United States of America.
Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer†
Article first published online: 5 MAY 2008
Published 2008 Wiley-Liss, Inc.
Volume 68, Issue 11, pages 1152–1164, 1 August 2008
How to Cite
Prueitt, R. L., Yi, M., Hudson, R. S., Wallace, T. A., Howe, T. M., Yfantis, H. G., Lee, Dong. H., Stephens, R. M., Liu, C.-G., Calin, G. A., Croce, C. M. and Ambs, S. (2008), Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer. Prostate, 68: 1152–1164. doi: 10.1002/pros.20786
- Issue published online: 17 JUN 2008
- Article first published online: 5 MAY 2008
- Manuscript Accepted: 1 APR 2008
- Manuscript Received: 22 OCT 2007
- Intramural Research Program of the NIH
- National Cancer Institute
- Center for Cancer Research
- National Institutes of Health grants. Grant Numbers: CA081534, CA128609
- prostate tumor;
- gene expression profile;
Perineural invasion (PNI) is the dominant pathway for local invasion in prostate cancer. To date, only few studies have investigated the molecular differences between prostate tumors with PNI and those without it.
To evaluate the involvement of both microRNAs and protein-coding genes in PNI, we determined their genome-wide expression with a custom microRNA microarray and Affymetrix GeneChips in 50 prostate adenocarcinomas with PNI and 7 without it. In situ hybridization (ISH) and immunohistochemistry was used to validate candidate genes.
Unsupervised classification of the 57 adenocarcinomas revealed two clusters of tumors with distinct global microRNA expression. One cluster contained all non-PNI tumors and a subgroup of PNI tumors. Significance analysis of microarray data yielded a list of microRNAs associated with PNI. At a false discovery rate (FDR) <10%, 19 microRNAs were higher expressed in PNI tumors than in non-PNI tumors. The most differently expressed microRNA was miR-224. ISH showed that this microRNA is expressed by perineural cancer cells. The analysis of protein-coding genes identified 34 transcripts that were differently expressed by PNI status (FDR < 10%). These transcripts were down-regulated in PNI tumors. Many of those encoded metallothioneins and proteins with mitochondrial localization and involvement in cell metabolism. Consistent with the microarray data, perineural cancer cells tended to have lower metallothionein expression by immunohistochemistry than nonperineural cancer cells.
Although preliminary, our findings suggest that alterations in microRNA expression, mitochondrial function, and cell metabolism occur at the transition from a noninvasive prostate tumor to a tumor with PNI. Prostate 68: 1152–1164, 2008. Published 2008 Wiley-Liss, Inc.