Supplementary Table 1

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Supplementary Table 1: Non-proteomic studies to discover biomarkers of prostate
cancer
Biomarker(s)
‡:
Samples†
IL-18BP
n = 67 cancer urine samples post DRE
and n = 37 healthy controls.
PCA3, TMPRSS2:ERG, and
Annexin-A3
n = 86 untreated prostate cancer
donors and n = 45 healthy controls.
Engrailed-2 (EN2)
n = 82 prostate cancer patients and n =
102 healthy controls-no need for DRE
with this marker.
c-MET receptor
n = 75 localized prostate cancer
donors, n = 81 metastatic prostate
cancer donors.
n = 16 prostate cancer urine samples, n
= 15 healthy controls.
δ-catenin
N-telopeptide of type-I collagen
n = 94 urine donors
Study design and Diagnostic/Prognostic
Utility‡
ELISA-based study. IL-18BP elevated in
prostate cancer urine compared to
controls. ROC AUC for IL-18 BP =
0.658.
qRT-PCR (PCA3, TMPRSS2:ERG)
and WB (Annexin-A3). Elevated levels
of Annexin-A3 protein in urine from
patients with PC, elevated levels of PCA3,
TMPRSS2: ERG transcripts ROC AUC
for panel = 0.84 (if PSA = 4-10 ng/ml)
and 0.856 (all patients).
ELISA/WB. EN2 elevated in prostate
cancer. Detection of prostate cancer,
sensitivity = 66%, specificity = 88.2%.
Results confirmed at a second centre.
ELISA. ROC AUC for detection of
metastatic disease = 0.90 (95% CI = 0.840.95).
WB-based study.. Increased δ-catenin
detects prostate cancer with 87.5%
specificity and 83.3% sensitivity.
Increased levels in the urine of prostate
cancer compared to controls (p<0.0005).
ELISA-based study. Increased uNTX
inversely correlated with overall patient
survival Elevated urinary NTx HR = 2.2.
(95% CI = 1.2-4.0).
Reference(s):
(1)
(2)
(3)
(4)
(5)
(6)
n = 411 urine donors.
ELISA-based study: Increased uNTX
inversely correlated with overall patient
survival High NTx levels associated with
a 4-6-fold increased risk of death, skeletal
related events and disease progression
compared to low levels (p < 0.001).
(7)
Alpha-methylacyl coenzyme-A
racemase
n = 26 urine donors.
(8)
Vascular Endothelial Growth
Factor (VEGF)
n = 100 prostate cancer patients.
Thymosin-β15
n = 61 untreated prostate cancer
patients, n = 46 prostatectomy
samples, 14 with androgen deprivation
therapy, and control groups (n = 52
normal patients, n = 15 with
genitourinary diseases, n = 81 with
non malignant prostate conditions and
n = 73 with other urological
conditions).
WB-based study. AMACR detected in 12
out of 12 donors with biopsy confirmed
adenocarcinoma, 5 out of 12 with no
cancer detected on biopsy and in 1 out of
2 with atypia on biopsy.
ELISA-study. Increased VEGF levels
correlate with decreased survival (p =
0.024). If VEGF > 28 pg/ml 60%
increased risk of death (HR = 1.62, p =
0.03).
ELISA-based study. At 40
(ng/dl)/microgram protein/mg creatinine
detection of PCa with 58% sensitivity and
94% specificity. Improves diagnostic
specificity of PSA monitoring.
ELISA-based study. Urinary prostatic
inhibin-like peptide high in benign
prostatic hyperplasia, and low in prostate
cancer.
ELISA-based study. CD105 elevated in
urine from biopsy proven cases versus
controls (p < 0.0014). ROC AUC = 0.72.
Predicts PC with a sensitivity of 73% and
a specificity of 63%
WB-Based Study. Annexin-A3 levels
drop within prostate cancer. Urine post
DRE used. Annexin-A3 levels and PSA
(11)
Prostatic inhibin-like peptide
Endoglin (CD105)
Annexin-A3
n = 99 prostate cancer urine samples, n
= 69 samples from radical
prostatectomy donors and n=20 from
patients classified as having low-risk
of prostate cancer.
n = 591 prostate cancer patients
recruited.
(9)
(10)
(12)
(13)
levels predicted prostate cancer with ROC
AUC = 0.82 (PSA = 2-6 ng/ml), 0.83
(PSA = 4-10 ng/ml) and = 0.81 (all
patients).
†All samples are human and urine unless otherwise specified; n numbers refer to number with
condition unless otherwise stated,
‡Abbreviations used for proteomic techniques are defined within the text and list of common
abbreviations.
1.
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prostate cancer cells and its levels in urine and serum correlate with tumor status. Int J Cancer. 2011 Jul
15;129(2):424-32.
2.
Cao DL, Ye DW, Zhang HL, Zhu Y, Wang YX, Yao XD. A multiplex model of combining gene-based,
protein-based, and metabolite-based with positive and negative markers in urine for the early diagnosis of
prostate cancer. Prostate. 2011 May 15;71(7):700-10.
3.
Morgan R, Boxall A, Bhatt A, Bailey M, Hindley R, Langley S, et al. Engrailed-2 (EN2): a tumor specific
urinary biomarker for the early diagnosis of prostate cancer. Clin Cancer Res. 2011 Mar 1;17(5):1090-8.
4.
Russo AL, Jedlicka K, Wernick M, McNally D, Kirk M, Sproull M, et al. Urine analysis and protein
networking identify met as a marker of metastatic prostate cancer. Clin Cancer Res. 2009 Jul 1;15(13):4292-8.
5.
Lu Q, Zhang J, Allison R, Gay H, Yang WX, Bhowmick NA, et al. Identification of extracellular deltacatenin accumulation for prostate cancer detection. Prostate. 2009 Mar 1;69(4):411-8.
6.
Rajpar S, Massard C, Laplanche A, Tournay E, Gross-Goupil M, Loriot Y, et al. Urinary N-telopeptide
(uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from
castration-resistant prostate cancer. Ann Oncol. 2010 Sep;21(9):1864-9.
7.
Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M, et al. Bone turnover markers as predictors of
skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005 Jan
5;97(1):59-69.
8.
Rogers CG, Yan G, Zha S, Gonzalgo ML, Isaacs WB, Luo J, et al. Prostate cancer detection on urinalysis
for alpha methylacyl coenzyme a racemase protein. J Urol. 2004 Oct;172(4 Pt 1):1501-3.
9.
Bok RA, Halabi S, Fei DT, Rodriquez CR, Hayes DF, Vogelzang NJ, et al. Vascular endothelial growth
factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate
cancer patients: a cancer and leukemia group B study. Cancer Res. 2001 Mar 15;61(6):2533-6.
10.
Hutchinson LM, Chang EL, Becker CM, Shih MC, Brice M, DeWolf WC, et al. Use of thymosin beta15 as
a urinary biomarker in human prostate cancer. Prostate. 2005 Jul 1;64(2):116-27.
11.
Teni TR, Sheth AR, Kamath MR, Sheth NA. Serum and urinary prostatic inhibin-like peptide in benign
prostatic hyperplasia and carcinoma of prostate. Cancer Lett. 1988 Dec 1;43(1-2):9-14.
12.
Fujita K, Ewing CM, Chan DY, Mangold LA, Partin AW, Isaacs WB, et al. Endoglin (CD105) as a urinary
and serum marker of prostate cancer. Int J Cancer. 2009 Feb 1;124(3):664-9.
13.
Schostak M, Schwall GP, Poznanovic S, Groebe K, Muller M, Messinger D, et al. Annexin A3 in urine: a
highly specific noninvasive marker for prostate cancer early detection. J Urol. 2009 Jan;181(1):343-53.
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