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Expression of microRNAs and protein‐coding genes associated with perineural invasion in prostate cancer
Author(s) -
Prueitt Robyn L.,
Yi Ming,
Hudson Robert S.,
Wallace Tiffany A.,
Howe Tiffany M.,
Yfantis Harris G.,
Lee Dong. H.,
Stephens Robert M.,
Liu ChangGong,
Calin George A.,
Croce Carlo M.,
Ambs Stefan
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20786
Subject(s) - perineural invasion , microrna , prostate cancer , biology , microarray analysis techniques , cancer research , immunohistochemistry , pathology , microarray , prostate , cancer , carcinogenesis , gene , gene expression , medicine , genetics
Background 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. Methods 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. Results 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. Conclusions 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.