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Protein‐coding and MicroRNA Biomarker Gene Panels Predictive of Clinical Recurrence in Prostate Cancer
Author(s) -
Moreno Carlos S,
Lai YuHeng,
Seth Arun,
Osunkoya Adeboye O,
Zhou Wei,
Petros John A,
Johnson Brent A,
Nam Robert K,
Barwick Benjamin G,
Abramovitz Mark,
Bouzyk Mark,
LeylandJones Brian R
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.361.2
Subject(s) - prostate cancer , microrna , prostatectomy , biochemical recurrence , biomarker , medicine , gene , gene expression profiling , oncology , cancer research , gene expression , cancer , bioinformatics , biology , genetics
An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery. To identify predictive biomarkers, we performed DASL expression profiling with a custom‐designed panel of 522 prostate cancer relevant genes on 71 FFPE radical prostatectomy specimens with long‐term outcome. We identified a panel of eight genes that could be used to predict recurrence (p = 0.001). Furthermore, this gene panel could separate patients with and without recurrence in the subset of 46 patients with Gleason 7 tumors (p = 0.022) for whom the decision regarding adjuvant therapy is particularly important and difficult. We also performed comprehensive miRNA profiling of these samples, and identified six miRNAs predictive of recurrence (p=0.001) for all 71 patients and for the subset of 46 Gleason 7 patients (p=0.032). Following promoter analysis of these miRNA genes, we determined that four of them are directly bound by SOX4 in chromatin immunoprecipitations, suggesting that SOX4 may regulate their expression. Among the potential downstream targets of these miRNA genes are several tumor suppressors involved in cell‐cycle arrest and apoptosis. It may therefore now be possible to increase the accuracy of prognostication for individual patients following radical prostatectomy using universally available archived specimens.