title: L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.
abstract: What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy.
  
  
  OBJECTIVE
  To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP).
  
  
  METHODS
  The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL.
  
  
  RESULTS
  DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015).
  
  
  CONCLUSIONS
  This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted.
authors.affiliation: 1st Department of Urology, Laiko General Hospital, University of Athens, School of Medicine, Athens, Greece. gkoutalellis@yahoo.com
authors.forename: Georgios
authors.initials: G
authors.lastname: Koutalellis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stravodimos
authors.forename: Margaritis
authors.initials: M
authors.lastname: Avgeris
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mavridis
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazaris
authors.forename: Constantinos
authors.initials: C
authors.lastname: Constantinides
mesh_terms: D000368:Aged; D004296:Dopa Decarboxylase / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D004296:Dopa Decarboxylase