Protein Patterns May Identify Ovarian Cancer
For interviews, animations, and other supplemental materials
on this study, please go to
http://cancer.gov/newscenter/benchmarks-vol2-issue2.
Scientists from the Food and Drug Administration (FDA) and the National Cancer
Institute (NCI) report today, in a special fast-tracked release in The Lancet*,
that patterns of proteins found in patients' blood serum may reflect the
presence of disease. In the study, scientists used serum proteins to detect
ovarian cancer, even at early stages. They report that this new diagnostic
concept is potentially applicable to any type of disease.
Using a test that can be completed in 30 minutes using blood that can be
obtained from a finger stick, researchers were able to differentiate between
serum samples taken from patients with ovarian cancer and those from unaffected
individuals.
The research, a joint effort between the FDA/NCI Clinical Proteomics Program and
Correlogic Systems Inc., unites two exciting disciplines: proteomics - the
study of the proteins inside cells - and artificial intelligence computer
programs.
The diagnostic test relied on software that is able to detect patterns of key
proteins in the blood. Using a sophisticated artificial intelligence computer
program developed by Correlogic, scientists were able to "train" the computer
to distinguish between patterns of small proteins found in the blood of cancer
patients vs. control samples. The artificial intelligence program identified a
pattern consisting of only a handful of proteins, among thousands, that could
be used to distinguish between women with ovarian cancer and women with
non-cancerous conditions.
"The idea that rather than a single biomarker, an entire pattern of proteins
contains important diagnostic information, is an exciting new paradigm," said
J. Carl Barrett, Ph.D., director of the NCI's Center for Cancer Research, which
oversees the proteomics program.
The scientists first used serum samples from known cancer patients and
unaffected individuals to establish proteomic patterns which were present at
different levels in the two groups. Once these patterns were identified, the
researchers compared them with the patterns of the same proteins in serum
samples from other patients with and without cancer. The researchers correctly
identified 50 out of 50 cancers and 63 of 66 non-cancer samples.
The researchers analyzed the serum proteins with mass spectroscopy, a technique
used to sort proteins and other molecules based on their weight and electrical
charge. The identity of the key proteins and the role they may play in cancer
is unknown, but being investigated.
An important finding was the ability to correctly identify, in a small sample of
patients, all stage I ovarian cancer cases. Currently, more than 80 percent of
ovarian cancer patients are diagnosed at a late clinical stage and have a 20
percent or less chance of survival at five years. In contrast, the 20 percent
of women diagnosed with early-stage disease have an excellent prognosis, with
over 95 percent alive at five years after diagnosis. The results of this study
indicate that proteomic technology may help clinicians diagnose the disease
much earlier than current methods.
The authors of the paper caution that further study is needed to confirm the
sensitivity and accuracy of this technique as a diagnostic tool. They hope that
by combining the proteomic approach with other methods of ovarian cancer
diagnosis, such as ultrasound, its accuracy can be further improved.
"Simple, accurate, and non-invasive methods for early detection of epithelial
ovarian cancer may improve quality of life and survival and reduce unnecessary
suffering for patients," said Kathryn Zoon, director of the Center for
Biologics Evaluation and Research (CBER) at the FDA. The majority of the
individuals included in the study had an increased risk of ovarian cancer, due
to a family history of the disease, or mutations in BRCA1 or BRCA2 genes, which
increase risk for both breast and ovarian cancers. Researchers on the study
from Northwestern University Medical School, Chicago, considered it important
to test the method in this population, as these are the women most in need of
effective screening options.
"The most important next goal is validating the promise of these results in
large, multi-institutional trials. Early detection means we can treat the
cancer before it has spread," said Lance Liotta, M.D., Ph.D., the senior
investigator on the study from the NCI's Center for Cancer Research. Such
trials are under way at the NCI, evaluating proteomics both alone and in
combination with current screening methods for ovarian cancer.
"We're particularly excited about the potential of this technique to diagnose
additional types of diseases. It may also be able to provide an early warning
of impending toxicity," said the first author of the study, Emanuel Petricoin,
Ph.D., of the FDA's CBER.
__* Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM,
Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA. Use of proteomic patterns
in serum to identify ovarian cancer. The Lancet 2002:261. Published on
www.thelancet.com
Feb. 8, 2002.
_____________________________________________________ For an in-depth interview
on clinical proteomics with the authors of this article, a background article
on future applications for this research, a 3D computer animation video
depicting various aspects of clinical proteomics, audio clips of the interview,
and photos and other materials, please go to:
http://cancer.gov/newscenter/benchmarks-vol2-issue2
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