Combination of three blood proteins may form basis for a biomarker screen for ovarian cancer
A new test measuring blood levels of three
proteins suggests there may be a molecular signature specific to
ovarian cancer that can be used to diagnose cases at an earlier
stage, according to an article in the August 15th issue of Cancer
research.
The current laboratory testing, which used
blood samples from patients in the US and international hospitals,
identified three proteins as a truncated form of transthyretin,
a fragment of ITIH4, and apolipoprotein A1.
"By identifying a select group of biomarkers
specific to ovarian cancer, we not only know the proteins we are
dealing with, but we can trace them back to alterations in the genetic
code of ovarian cancer cells," said Daniel W. Chan, PhD, a
coauthor of the article. "We are focusing on the markers for
which we have good biological reasoning behind their selection,
and hope to expand the panel of markers to catch as many variations
in ovarian cancer proteins as possible."
The researchers emphasized that the test
will not be commercially available for screening the population
at large until completion of further validation studies in larger
groups of patients. And even then, Chan noted, it is never going
to be possible for a blood test to correctly diagnose 100 percent
of cancerous tumors 100 percent of the time. "The goal is to
come as close as possible to that by using this test in combination
with other available diagnostic tools."
The authors believe, however, that with some
refinements it may already have use for helping determine whether
a pelvic mass is ovarian cancer.
In a systematic search to find the most promising
blood proteins for their test, the scientists conducted a multicenter
study and screened a total of 195 blood samples from two groups
of ovarian cancer patients, healthy people, and patients with benign
ovarian tumors. A sophisticated bioinformatics program was used
to select proteins present at unusually high or low levels in ovarian
cancer samples compared with normal or benign.
Samples in the two groups were analyzed separately
to account for differences in patient populations and sample collection
techniques. Then, researchers compared protein profile results in
these two groups and ultimately narrowed the search for potential
marker candidates to the three proteins, one of which (ITIH4) is
commonly found at high levels in ovarian cancer and the other two
at lower levels.
"Typically, only half of early-stage
ovarian cancer patients have high blood levels of a standard marker
called CA125," said Zhen Zhang, PhD, lead author of the study,
“But combining CA125 with our new markers may improve early detection
capabilities."
The new proteins were screened against a
separate collection of blood samples from patients with normal and
cancerous tissues. Of 23 patients with early-stage ovarian cancer,
the three protein markers plus CA125 correctly identified cancer
74 percent of the time (17 of 23) compared to 65 percent (15 of
23) with CA125 alone.
Although the sample size was too small for
this difference to be statistically significant, the scientists
conducted further studies lowering the cutoff value for CA125 to
below current standards. The new test plus CA125 as well as CA125
alone detected 83 percent (19 of 23) of the cancers. In addition,
the new test plus CA125 correctly identified healthy samples 94
percent of the time (59 of 63) compared with 52 percent (33 of 63)
for CA125 alone.
To verify that the candidate markers were
specific to ovarian cancer, the scientists also compared results
of the protein profiles with a separate group of blood samples from
142 patients with ovarian, breast, colon, or prostate cancer and
healthy people. Protein markers from the ovarian cancer samples
matched those from the other two groups of blood samples. Breast,
colon and prostate cancer samples exhibited levels of the three
proteins closer to those of normal patients, indicating that the
markers are exclusive to ovarian cancer.
The scientists will conduct further studies
to map all three proteins to the genetic pathways linked to ovarian
cancer development and combine the blood test with radiologic tools
such as ultrasound. They also will search for more proteins to add
to the current panel of markers.
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