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1 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287.
aAuthor for correspondence.
Background: Surface-enhanced laser desorption/ionization (SELDI) is an affinity-based mass spectrometric method in which proteins of interest are selectively adsorbed to a chemically modified surface on a biochip, whereas impurities are removed by washing with buffer. This technology allows sensitive and high-throughput protein profiling of complex biological specimens.
Methods: We screened for potential tumor biomarkers in 169 serum samples, including samples from a cancer group of 103 breast cancer patients at different clinical stages [stage 0 (n = 4), stage I (n = 38), stage II (n = 37), and stage III (n = 24)], from a control group of 41 healthy women, and from 25 patients with benign breast diseases. Diluted serum samples were applied to immobilized metal affinity capture Ciphergen ProteinChip® Arrays previously activated with Ni2+. Proteins bound to the chelated metal were analyzed on a ProteinChip Reader Model PBS II. Complex protein profiles of different diagnostic groups were compared and analyzed using the ProPeak software package.
Results: A panel of three biomarkers was selected based on their collective contribution to the optimal separation between stage 0–I breast cancer patients and noncancer controls. The same separation was observed using independent test data from stage II–III breast cancer patients. Bootstrap cross-validation demonstrated that a sensitivity of 93% for all cancer patients and a specificity of 91% for all controls were achieved by a composite index derived by multivariate logistic regression using the three selected biomarkers.
Conclusions: Proteomics approaches such as SELDI mass spectrometry, in conjunction with bioinformatics tools, could greatly facilitate the discovery of new and better biomarkers. The high sensitivity and specificity achieved by the combined use of the selected biomarkers show great potential for the early detection of breast cancer.
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T. C.W. Poon, T.-T. Yip, A. T.C. Chan, C. Yip, V. Yip, T. S.K. Mok, C. C.Y. Lee, T. W.T. Leung, S. K.W. Ho, and P. J. Johnson Comprehensive Proteomic Profiling Identifies Serum Proteomic Signatures for Detection of Hepatocellular Carcinoma and Its Subtypes Clin. Chem., May 1, 2003; 49(5): 752 - 760. [Abstract] [Full Text] [PDF]
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H. Hondermarck Breast Cancer: When Proteomics Challenges Biological Complexity Mol. Cell. Proteomics, May 1, 2003; 2(5): 281 - 291. [Abstract] [Full Text] [PDF]
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E. F. Petricoin and L. A. Liotta Mass Spectrometry-based Diagnostics: The Upcoming Revolution in Disease Detection Clin. Chem., April 1, 2003; 49(4): 533 - 534. [Full Text] [PDF]
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 W. A. Colburn Biomarkers in Drug Discovery and Development: From Target Identification through Drug Marketing J. Clin. Pharmacol., April 1, 2003; 43(4): 329 - 341. [Abstract] [Full Text] [PDF]
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E. F. Petricoin III and L. A. Liotta RESPONSE: Re: Serum Proteomic Patterns for Detection of Prostate Cancer J Natl Cancer Inst, March 19, 2003; 95(6): 490 - 491. [Full Text] [PDF]
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