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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