A combination of three proteins found at high levels
in urine can accurately detect early-stage
pancreatic cancer, researchers at the Barts Cancer
Institute (BCI) have shown. The discovery could lead
to a non-invasive, inexpensive test to screen people
at high risk of developing the disease.
Dr Tatjana Crnogorac-Jurcevic's group has shown that
the three-protein ‘signature’ can both identify the
most common form of pancreatic cancer when still in
its early stages - and distinguish between this
cancer and the inflammatory condition chronic
pancreatitis, which can be hard to tell apart.
The study, published in the journal Clinical Cancer
Research, was funded by the UK charity, the
Pancreatic Cancer Research Fund. It looked at 488
urine samples: 192 from patients known to have
pancreatic cancer, 92 from patients with chronic
pancreatitis and 87 from healthy volunteers. A
further 117 samples from patients with other benign
and malignant liver and gall bladder conditions were
used for further validation.
Around 1500 proteins were found in the urine
samples, with approximately half being common to
both male and female volunteers.
Of these, three proteins - LYVE1, REG1A and TFF1 -
were selected for closer examination, based on
biological information and performance in
statistical analysis.
Patients with pancreatic cancer were found to have
increased levels of each of the three proteins when
compared to urine samples from healthy patients,
while patients suffering from chronic pancreatitis
had significantly lower levels than cancer patients.
When combined, the three proteins formed a robust
panel that can detect patients with stages I-II
pancreatic cancer with over 90 per cent accuracy.
With few specific symptoms even at a later stage of
the disease, more than 80 per cent of people with
pancreatic cancer are diagnosed when the cancer has
already spread. This means they are not eligible for
surgery to remove the tumour - currently the only
potentially curative treatment.
The five-year survival rate for pancreatic cancer is
the lowest of any common cancer, standing at 3 per
cent. This figure has barely improved in 40 years.
There is no early diagnostic test available.
Lead researcher, Dr Tatjana Crnogorac-Jurcevic,
said: “We’ve always been keen to develop a
diagnostic test in urine as it has several
advantages over using blood. It’s an inert and far
less complex fluid than blood and can be repeatedly
and non-invasively tested. It took a while to secure
proof of principle funding in 2008 to look at
biomarkers in urine, but it’s been worth the wait
for these results.
This is a biomarker panel with good specificity and
sensitivity and we’re hopeful that a simple,
inexpensive test can be developed and be in clinical
use within the next few years.”
Although there is no universal cause of pancreatic
cancer, people at higher risk of developing the
disease include those with a family history of
pancreatic cancer, heavy smokers, the obese and
people over 50 years with new-onset diabetes.
The team is hoping to conduct further tests on urine
samples from people in high risk groups, to further
validate the study findings. Dr Crnogorac-Jurcevic
is also keen to access samples of urine collected
from volunteers over a period of 5-10 years. By
examining samples from donors who went on to develop
pancreatic cancer, this ‘longitudinal’ information
will allow the researchers to see if the 3-biomarker
signature is present during the latency period – the
time between the genetic changes that will cause the
cancer to develop and the clinical presentation.
“For a cancer with no early stage symptoms, it’s a
huge challenge to diagnose pancreatic cancer sooner,
but if we can, then we can make a big difference to
survival rates,” says co-author and Director of
Barts Cancer Institute, Professor Nick Lemoine.
“With pancreatic cancer, patients are usually
diagnosed when the cancer is already at a terminal
stage, but if diagnosed at stage 2, the survival
rate is 20 per cent, and at stage 1, the survival
rate for patients with very small tumours can
increase up to 60 per cent.”
CEO of the Pancreatic Cancer Research Fund, Maggie
Blanks, said: “This is an exciting finding and we
hope to see this research taken forward into a much
needed early diagnostic test. Early diagnosis is an
important part of our overall efforts against this
aggressive cancer, alongside developing new
treatments to tackle the disease once diagnosis is
made. It underlines the importance of increased
research efforts to help improve survival rates.
“Many of the urine samples from healthy individuals
tested by Tanja’s team were donated from the
charity’s own supporter community, and I know they
will be extremely proud that they have directly
contributed to research progress in ways that go
beyond traditional financial support.”
For more information
Clinical Cancer Research
Identification of a Three-Biomarker Panel in Urine
for Early Detection of Pancreatic Adenocarcinoma
Barts Cancer Institute
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