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Testing for PCa using proteomic
patterns. (December 2002)
Proteomics: A new blood test holds much
promise for PC diagnosis. Proteomics is the new boy on the block and we
are going to hear more and more from this new field of science. Basically,
"proteomics" refers to the study of the "proteome", the sum total of all
of the body's proteins. When DNA is "read" instructions are sent out from
the nucleus to the protein manufacturing plants (ribosomes) in the
cytoplasm, which then assembly amino acids into complex molecules, i.e.,
proteins. The amino acid chain is quickly folded and either dispatched for
internal use in the cell or exported. The proteins of interest in this
discussion are those secreted into the serum. The basic premise of the
test is that any organ perfused by blood can make unique contributions
into the totality of circulating proteins. This test, using a technique
called mass spectroscopy, then attempts to identify a characteristic
"protein fingerprint" that would reveal the presence of, for example,
prostate cancer.
The LANCET, October16, 2002, presented the first report of applying
proteomic pattern analysis for the detection of prostate cancer. The
search is NOT for PSA, but for the protein PATTERN characteristic of
prostate cancer. The analysis of each sample queried 15,200 points of
interest in the serum. The preliminary development work on the test
revealed that the optimal discrimination between benign and malignant
prostate conditions could be made by comparing a combination of seven of
those points. The article reads, "We have combined...serum profiling with
artificial intelligence to move beyond single-marker analysis to proteomic
pattern analysis."
The basis of the study: The prostate screening trial study group involved
266 men who were asymptomatic with PSA's of 4 or higher (or men with
suspicious DREs with any level of PSA) who then underwent a sextant
biopsy. The quest was to predict from the baseline protein profile
analysis which men would have cancer diagnosed in their biopsies.
The results of the study: Regarding the 38 men who had PC on biopsy, the
test correctly predicted cancer in 36 (sensitivity = 95%). All of the
seven men who had Stage I PC all were correctly predicted to have
malignancy. Among the 228 men whose biopsies were negative 51 were
INCORRECTLY predicted have PC, thus giving the test an 18% false positive
rate. In men with benign biopsies whose PSA's were 4-10, the false
positive rate was 29%, yielding a 71% specificity for the test in this
range.
There is no intention for this test to substitute for a biopsy diagnosis,
nor is it sufficiently developed for PC screening. But it is first step in
an entirely new direction in PC diagnosis and when further refined may
have much to offer.
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