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Abstract
Mammography remains the diagnostic test of choice for breast cancer, but 20% of cancers
still go undetected. Many serum biomarkers have been reported for breast cancer but
none have proven to represent effective diagnostic strategies. ProteinChip® mass spectrometry
is an innovative technology that searches the proteome for differentially expressed
proteins, allowing for the creation of a panel or profile of biomarkers. The objective
of this study was to construct unique cancer-associated serum profiles that, combined
with a classification algorithm, would enhance the detection of breast cancer. Pretreatment
serum samples from 134 female patients (45 with cancer, 42 with benign disease, 47
normal) were procured prospectively following institutional review board—approved
protocols. Proteins were denatured, applied onto ProteinChip® affinity surfaces, and
subjected to surface enhanced laser desorption/ionization (SELDI) time-of-flight mass
spectrometry. The SELDI output was analyzed using Biomarker Pattern Software to develop
a classification tree based on group-specific protein profiles. The cross-validation
analysis of cancer versus normal revealed sensitivity and specificity rates of 80%
and 79%, and for cancer versus benign disease, 78% and 83%, respectively. When 2 different
chip surfaces were combined the sensitivity and specificity increased to 90% and 93%,
respectively. The sensitivity and specificity of this technique are comparable to
those of mammography and, if confirmed in a larger study, this technique could provide
the means toward development of a simple blood test to aid in the early detection
of breast cancer. The combination of SELDI ProteinChip® mass spectrometry and a classification-
and regression-tree algorithm has the potential to use serum protein expression profiles
for detection and diagnosis of breast cancer.
Key words
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Article info
Publication history
Accepted:
July 30,
2003
Received in revised form:
July 28,
2003
Received:
June 23,
2003
Identification
Copyright
© 2003 Elsevier Inc. Published by Elsevier Inc. All rights reserved.