PURPOSE: Because Gleason grade 4/5 @entity5 is the primary cause of failure to cure @entity263 , we examined the molecular profiles of this high grade @entity5 in search of potentially new therapeutic interventions as well as better serum markers than @entity1486 . MATERIALS AND METHODS: We compared the gene expressions in fresh frozen tissues from 9 @entity1 with Gleason grade 4/5 @entity5 to 8 @entity1 with @entity1067 ( @entity1067 ) treated with radical retropubic prostatectomy. Labeled complementary RNA from each of the 17 tissues was applied to HuGeneFL probe arrays representing approximately 6,800 genes (Affymetrix, Inc., Santa Clara, @entity7452 ). After removing all genes undetectable in @entity1067 and grade 4/5 @entity5 , and transforming the data into a parametric distribution, we chose only those up and down-regulated genes with a p difference in fluorescence between grade 4/5 @entity5 and @entity1067 of p <0.0005. This value reduced the data set to 40 up-regulated and 111 down-regulated genes. We then eliminated all genes that were not expressed in all 8 @entity1067 and 9 grade 4/5 tissues, which produced a final set of 86 genes, of which 22 were up-regulated and 64 were down-regulated. RESULTS: Cluster analysis cleanly separated @entity1 with grade 4/5 @entity5 from those with @entity1067 . Only 17 of the 86 candidate genes (20%) were known to be @entity263 related and 42 (49%) were related to other @entity5 . The most up-regulated gene is Hepsin, a trypsin-like @entity563 protease with its enzyme catalytic domain oriented extracellularly. Prostate specific membrane antigen is the second most up-regulated gene (all other reports on prostate specific membrane antigen have been at the protein level). The genes for @entity1486 ( @entity16914 ) and @entity1 @entity27656 ( @entity14958 ) showed equivalent expression levels 10 times the average of other genes. Complete lists of all 22 up-regulated genes and 64 down-regulated genes, together with their locus on the chromosome, are presented in rank order. CONCLUSIONS: We characterize for the first time 64 down-regulated and 22 up-regulated genes in Gleason grade 4/5 @entity5 , using the gene profile from @entity1067 as control tissue. A number of interesting new genes, previously undescribed in @entity263 , are presented as possibilities for further study.

Molecular genetic profiling of XXXX compared to @entity1067 .

@entity1 :: ('9606', 'Species') :: ['human', 'men'] @entity14958 :: ('58164', 'Gene') :: ['hK2'] @entity16914 :: ('3850', 'Gene') :: ['hK3'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'cancer'] @entity1067 :: ('MESH:D011470', 'Disease') :: ['benign prostatic hyperplasia', 'BPH'] @entity7452 :: ('MESH:D004670', 'Disease') :: ['California'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity27656 :: ('3817', 'Gene') :: ['glandular kallikrein2'] @entity1486 :: ('354', 'Gene') :: ['prostate specific antigen']
@entity263 :: (MESH:D011471,Disease) :: ['Gleason grade 4/5 prostate cancers']
