Biology Reference
In-Depth Information
that for detecting any prostate cancer, PSA cutoff
values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded
sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%
and speci
The question that needs to be addressed is why
these and other potential biomarkers failed in
achieving adequate sensitivity and speci
city and
are not accepted as clinical tests. The answer is
not an easy one because we are dealing with detect-
ing cancer at an early stage in humans with
different characteristics such as age, sex, and
ethnicity. Another important fact should also be
considered:
cities of 38.9%, 72.5%, 86.7%, and
93.8%, respectively. The authors reported that
“
there is no cut point of PSA level with simulta-
neous high sensitivity and high speci
city for
monitoring healthy men for prostate cancer.
”
The majority of PSA elevations between 4
e
10
ng/ml are due to prostatic hyperplasia rather
than the malignancy leading to many unneces-
sary biopsies.
Cancer antigen (CA) 15-3 and cancer antigen
CA 27.29 are two well-known biomarkers for
monitoring breast cancer. CA 15-3 is a blood
test given during or after treatment for breast
cancer. It is most useful for monitoring advanced
breast cancer and response to treatment. CA 15-3
and CA 27.29 are not screening tests; they are
tumor marker tests that assist in tracking cancers
that overproduce CA 15-3 and CA 27.29. Only
about 30% of patients with localized breast cancer
will have increased levels of CA 15-3
9
;many
patients with liver and breast diseases show
elevated levels. Another malignancy of the repro-
ductive system, ovarian cancer, is detected using
a combination of pelvic examination, transvagi-
nal ultrasonography, and laparoscopy.
10
There
is no speci
in biomarker studies, the aim is to
find a protein or a metabolite (that is probably at
an extremely low concentration level) among thou-
sands of proteins and metabolites. This goal is
extremely challenging. One of the major reasons
that proteomic and metabolomic studies over the
past decade have failed to discover molecules to
replace existing clinical tests is due to errors in either
study design and/or experimental execution.
STU
DY DESIGN AND EXECUT
ION
The search for biomarkers for any disease and
especially cancer requires careful consideration
of different aspects of a study prior to its initia-
tion. These include study design, experimental
execution, personnel, and instrumentation.
Study Design
The design of a biomarker discovery project
should consider the following steps: disease of
interest, the number of patients and matched
controls, selection of patients
c and sensitive diagnostic test for
ovarian cancer; although CA 125 is used to distin-
guish between benign and malignant diseases,
10
it is not a reliable biomarker because it is affected
by other factors and 20% of ovarian cancer
patients do not express CA 125.
11
The above-mentioned examples show that to
date there are no 100% sensitive and speci
'
sex, age, and
ethnicity, type of samples (tissue, blood, serum,
plasma), what class of molecule(s) to measure
(proteins, metabolites, or nucleotides), and
whether the goal of the search is for a pro
c
biomarkers for different types of cancer. Does
a combination of biomarkers give better sensi-
tivity and speci
le or
a single discriminating molecule. If the study is
focused on cancer, the type and stage of cancer
must be speci
city? The answer is yes. For
example, Hortsmann et al.
12
studied the effect
of using a combination of bladder cancer bio-
markers on sensitivity and speci
ed.
city. Although
none of the combinations resulted in 100% sensi-
tivity and speci
Study Execution
Study execution deals with experimental
parameters that can affect the results. These
city, the sensitivity improved
over using a single biomarker.
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