Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer Margaritis Avgeris a , Georgios Koutalellis b , Emmanuel G. Fragoulis a , Andreas Scorilas a, ⁎ a Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece b First Department of Urology, “Laiko” Hospital, Faculty of Medicine, University of Athens, Athens, Greece Received 30 December 2007; received in revised form 20 April 2008; accepted 24 April 2008 Available online 10 June 2008 Abstract Background: L-Dopa decarboxylase (DDC) is a pyridoxal 5′-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Methods: Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green ® chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. Results: DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p b 0.001). Logistic regression and ROC analysis have demonstrated that the DDC expression has significant discriminatory value between CaP and BPH (p b 0.001). DDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p = 0.022) as well as in advanced stage patients (p = 0.032). Conclusions: Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer. © 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Keywords: L-Dopa decarboxylase; DDC; Prostate cancer; Tumor biomarkers; PSA; Real-time PCR; LNCaP; PC3 Introduction Prostate tumors are classified among the commonest diseases affecting men, mainly of the middle and advanced ages [1]. The incidence of occurrence of histologically observed benign prostate hyperplasia (BPH) is approximately 50% for the men of 51–60-year old and 90% for those of 85 years of age [2,3]. Prostate cancer (CaP) is the most frequently diagnosed non-cutaneous malignancy in the men population in many Western countries and the second leading cause of cancer- related deaths, following lung cancer, in the USA [4,5]. Prostate-specific antigen (PSA), also known as human Kallikrein 3 (KLK3), is a prostate secreted serine protease, widely used as a serum biomarker for the early detection and further progression of prostate cancer [6,7]. However, serum PSA concentration is non-specific for prostate cancer and could, also, be increased in other non-malignant prostate abnormal- ities, such as BPH, prostatic intraepithelial neoplasia (PIN), acute or chronic prostatitis, inflammation and trauma of the prostate gland [8,9]. Approximately 20% of CaP patients present with PSA concentrations lower than 4 ng/mL, while only about 30% of men with concentrations between 4 and 10 ng/mL, belonging to the so-called PSA “gray zone”, will develop CaP [10,11]. Although several calculated parameters, such as PSA transition zone density, PSA velocity and age- related PSA, as well as measurements of the rate of free PSA (fPSA) to total PSA (tPSA) corresponding to the percentage of free PSA (% fPSA), particularly in the tPSA “gray zone”, have been recruited to improve PSA specificity, these have been only partially successful [12–19]. Prostate is an androgen-regulated organ, in which the role of androgens, via the androgen receptor (AR), is well established in the development and the function of the gland as well as the Available online at www.sciencedirect.com Clinical Biochemistry 41 (2008) 1140 – 1149 ⁎ Corresponding author. E-mail address: ascorilas@biol.uoa.gr (A. Scorilas). 0009-9120/$ - see front matter © 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2008.04.026