Determination of amino acids in urine of patients with
prostate cancer and benign prostate growth
Wiktor D. Sroka
a
, Berin A. Boughton
e
, Priyanka Reddy
e
, Ute Roessner
e
,
Piotr Slupski
c
, Piotr Jarzemski
c
, Anita Dąbrowska
b
,
Michal J. Markuszewski
d
and Michal P. Marszall
a
Prostate cancer is the leading type of cancer diagnosed in
men. Serum prostate-specific antigen levels and digital
rectal exam are far from perfect when it comes to
differentiation of patients with prostate cancer and benign
prostatic hyperplasia. In this study, we attempt to determine
whether amino acids can be used as prostate cancer
biomarkers. Concentrations of derivatized amino acids and
amines were quantified by liquid chromatography tandem
mass spectrometry. A total of 100 urine samples from the
two groups including samples provided before and after
prostate massage were examined quantitatively for amino
acid and amine concentrations with 50 urine samples
collected from cancer patients and 50 samples from
patients diagnosed with benign prostatic hyperplasia.
Arginine, homoserine, and proline were more abundant in
urine samples of cancer patients compared with arginine,
homoserine, and proline levels determined in urine
collected from patients with benign growth. We also show
that sarcosine is not a definitive indicator of prostate cancer
when analyzed in urine samples collected either before or
after prostate massage. European Journal of Cancer
Prevention 00:000–000 Copyright © 2016 Wolters Kluwer
Health, Inc. All rights reserved.
European Journal of Cancer Prevention 2016, 00:000–000
Keywords: amino acids, benign prostatic hyperplasia, biomarker, cancer,
prostate
Departments of
a
Medicinal Chemistry,
b
Theoretical Foundations of Biomedical
Sciences and Medical Informatics,
c
Department of Urology, Jan Biziel Hospital,
Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus
University in Torun,
d
Department of Biopharmaceutics and Pharmacodynamics,
Medical University of Gdansk, Gdansk, Poland and
e
Metabolomics Australia,
School of BioSciences, The University of Melbourne, Parkville, Victoria, Australia
Correspondence to Michal P. Marszall, PhD, Department of Medicinal Chemistry,
Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus
University in Torun, ul. Jurasza 2, 85-094 Bydgoszcz, Poland
Tel: + 48 52 585 3540; fax: + 48 52 585 3804; e-mail: mmars@cm.umk.pl
Received 15 September 2015 Accepted 7 February 2016
Introduction
Prostate cancer (PCa) is the second most common cause
of cancer-related death and leading type of cancer diag-
nosed in men. Currently, for screening purposes, serum
prostate-specific antigen (PSA) levels and digital rectal
examination are used to determine whether a patient
presents with PCa. PSA levels can be useful in differ-
entiating healthy and sick patients, but it needs to be
noted that the sensitivity and specificity of this test are
poor. Although PSA testing can diagnose more men with
PCa, PSA is not a perfect biomarker. PSA is specific to
the prostate gland, not to PCa; patients diagnosed for
example with benign prostatic hyperplasia (BPH) can
also present with elevated serum PSA levels (Lilja et al.,
2008; Wolf et al., 2010).
Monitoring changes in certain metabolites may be a way
to detect early stages of carcinogenesis, predict cancer
stage, or monitor the treatment response. The new bio-
marker may improve the diagnostic process by helping
physicians to more accurately diagnose patients and also
improve a patient’s comfort during the procedure by
reducing the number of invasive procedures (Birkemeyer
et al., 2005; Denkert et al., 2006; Wang et al., 2010;
Serkova et al., 2011).
The aims of our research were to measure changes in
amine and amino acid concentrations in urine from
samples collected in the morning, before and after pros-
tate massage, identify and quantify a number of amino
acids in urine with the aim of testing the use of sarcosine
as a definitive marker of PCa, or to find an improved
biomarker (Sreekumar et al., 2009).
Methods
A total of 50 individuals were recruited into two main
groups of patients – a cancer group of 25 patients diag-
nosed with PCa qualifying for radical prostatectomy and a
second BPH group of 25 patients qualifying for transur-
ethral resection of the prostate with no evidence of
malignancy, but diagnosed with BPH. Amino acids and
biogenic amines were measured according to Boughton
et al. (2011). Concentrations of derivatized amino acids
were quantified by liquid chromatography mass spectro-
metry using an Agilent 1200 LC-system coupled to an
Agilent 6410 ESI-QqQ-MS (Santa Clara, California,
USA) by comparison with external calibration curves.
More detailed information can be found in the
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of this
article on the journal's website (www.eurjcancerprev.com).
Short paper 1
0959-8278 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/CEJ.0000000000000248
Copyright r 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.