title: Protein-coding and microRNA biomarkers of recurrence of prostate cancer following radical prostatectomy.
abstract: An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery to determine whether immediate adjuvant therapy is warranted. To identify biomarkers predictive of biochemical recurrence, we isolated the RNA from 70 formalin-fixed, paraffin-embedded radical prostatectomy specimens with known long-term outcomes to perform DASL expression profiling with a custom panel that we designed of 522 prostate cancer-relevant genes. We identified a panel of 10 protein-coding genes and two miRNA genes (RAD23B, FBP1, TNFRSF1A, CCNG2, NOTCH3, ETV1, BID, SIM2, LETMD1, ANXA1, miR-519d, and miR-647) that could be used to separate patients with and without biochemical recurrence (P < 0.001), as well as for the subset of 42 Gleason score 7 patients (P < 0.001). We performed an independent validation analysis on 40 samples and found that the biomarker panel was also significant at prediction of biochemical recurrence for all cases (P = 0.013) and for a subset of 19 Gleason score 7 cases (P = 0.010), both of which were adjusted for relevant clinical information including T-stage, prostate-specific antigen, and Gleason score. Importantly, these biomarkers could significantly predict clinical recurrence for Gleason score 7 patients. These biomarkers may increase the accuracy of prognostication following radical prostatectomy using formalin-fixed specimens.
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.forename: Brent A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.forename: Yu-Heng
authors.initials: YH
authors.lastname: Lai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Mark
authors.initials: M
authors.lastname: Abramovitz
authors.forename: Mingjing
authors.initials: M
authors.lastname: Xia
authors.forename: Mark B
authors.initials: MB
authors.lastname: Bouzyk
authors.forename: Robert K
authors.initials: RK
authors.lastname: Nam
authors.forename: Linda
authors.initials: L
authors.lastname: Sugar
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanimirovic
authors.forename: Daron J
authors.initials: DJ
authors.lastname: Williams
authors.forename: Brian R
authors.initials: BR
authors.lastname: Leyland-Jones
authors.forename: Arun K
authors.initials: AK
authors.lastname: Seth
authors.forename: John A
authors.initials: JA
authors.lastname: Petros
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D011183:Postoperative Complications; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000601:surgery*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen