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Received on May 20, 2005
Accepted on September 7, 2005
Proteomics and Protein Markers |
1 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
2 National Cancer Institute of Milan, Italy
3 University of Texas, MD Anderson Cancer Center, Houston, TX
4 Ciphergen Biosystems, Inc., Fremont, CA
5 Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
6 Oncology, Johns Hopkins Medical Institutions, Baltimore, MD
Background: We previously selected a panel of 3 breast cancer biomarkers (BC1, BC2, and BC3) from serum samples collected at a single hospital based on their collective contribution to the optimal separation of breast cancer patients and noncancer controls by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The identities and general applicability of these markers, however, were unknown. In this study, we performed protein expression profiling on samples obtained from a second hospital, included a greater number of ductal carcinoma in situ (DCIS) cases, and performed purification and identification of the 2 confirmed markers.
Methods: Using a case-control study design, we performed protein expression profiling on serum samples from the National Cancer Institute (Milan, Italy). The validation sample cohort consisted of 61 women with locally invasive breast cancer, 32 with DCIS, 37 with various benign breast diseases (including 13 atypical), and 46 age-matched apparently healthy women (age range, 44-68 years). Validated biomarkers were purified and identified with serial chromatography, 1-dimensional gel electrophoresis, in-gel ASP-N digestion, peptide mass fingerprinting, and tandem mass peptide sequencing.
Results: The BC3 and BC2 expression patterns in this sample set were consistent with the first study sample set. BC3 and BC2 were identified to be complement component C3adesArg and a C-terminal-truncated form of C3adesArg, respectively.
Conclusions: Evaluation of biomarkers in independent sample sets can help determine the broader utility of candidate markers, and protein identification permits understanding of their molecular basis. C3adesArg appears to lack specificity among patients with benign diseases, limiting its utility as a stand-alone tumor marker, but it may still be useful in a multimarker panel for early detection of breast cancer.
The following articles in journals at HighWire Press have cited this article:
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  L. Chung, A. E. Nelson, K. K. Y. Ho, and R. C. Baxter Proteomic Profiling of Growth Hormone-Responsive Proteins in Human Peripheral Blood Leukocytes J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 3038 - 3043. [Abstract] [Full Text] [PDF]
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 B. A. ZEIDAN, R. I. CUTRESS, N. MURRAY, G. R. COULTON, C. HASTIE, G. PACKHAM, and P. A. TOWNSEND Proteomic Analysis of Archival Breast Cancer Serum Cancer Genomics Proteomics, May 1, 2009; 6(3): 141 - 147. [Abstract] [Full Text] [PDF]
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 T. Hori, Y. Naishiro, H. Sohma, N. Suzuki, N. Hatakeyama, M. Yamamoto, T. Sonoda, Y. Mizue, K. Imai, H. Tsutsumi, et al. CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease Blood, April 15, 2008; 111(8): 4403 - 4412. [Abstract] [Full Text] [PDF]
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 H. Zhang and D. W. Chan Cancer Biomarker Discovery in Plasma Using a Tissue-targeted Proteomic Approach Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1915 - 1917. [Full Text] [PDF]
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 J. F. Timms, E. Arslan-Low, A. Gentry-Maharaj, Z. Luo, D. T'Jampens, V. N. Podust, J. Ford, E. T. Fung, A. Gammerman, I. Jacobs, et al. Preanalytic Influence of Sample Handling on SELDI-TOF Serum Protein Profiles Clin. Chem., April 1, 2007; 53(4): 645 - 656. [Abstract] [Full Text] [PDF]
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 T. Nakagawa, S. K. Huang, S. R. Martinez, A. N. Tran, D. Elashoff, X. Ye, R. R. Turner, A. E. Giuliano, and D. S.B. Hoon Proteomic Profiling of Primary Breast Cancer Predicts Axillary Lymph Node Metastasis Cancer Res., December 15, 2006; 66(24): 11825 - 11830. [Abstract] [Full Text] [PDF]
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 D. Nedelkov, U. A. Kiernan, E. E. Niederkofler, K. A. Tubbs, and R. W. Nelson Population Proteomics: The Concept, Attributes, and Potential for Cancer Biomarker Research Mol. Cell. Proteomics, October 1, 2006; 5(10): 1811 - 1818. [Abstract] [Full Text] [PDF]
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 P. Du, W. A. Kibbe, and S. M. Lin Improved peak detection in mass spectrum by incorporating continuous wavelet transform-based pattern matching Bioinformatics, September 1, 2006; 22(17): 2059 - 2065. [Abstract] [Full Text] [PDF]
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G. L. Hortin The MALDI-TOF Mass Spectrometric View of the Plasma Proteome and Peptidome Clin. Chem., July 1, 2006; 52(7): 1223 - 1237. [Abstract] [Full Text] [PDF]
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G. L. Hortin, S. A. Jortani, J. C. Ritchie Jr, R. Valdes Jr, and D. W. Chan Proteomics: A New Diagnostic Frontier Clin. Chem., July 1, 2006; 52(7): 1218 - 1222. [Abstract] [Full Text] [PDF]
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P. Kepper, R. Reinhardt, A. Dahl, H. Lehrach, and S. Sauer Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Analysis of DNA on Microarrays Clin. Chem., July 1, 2006; 52(7): 1303 - 1310. [Abstract] [Full Text] [PDF]
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E. P. Diamandis Serum Proteomic Profiling by Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry for Cancer Diagnosis: Next Steps Cancer Res., June 1, 2006; 66(11): 5540 - 5541. [Full Text] [PDF]
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E. P. Diamandis Validation of breast cancer biomarkers identified by mass spectrometry. Clin. Chem., April 1, 2006; 52(4): 771 - 772. [Full Text] [PDF]
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J. Li, Z. Zhang, and D. W. Chan Validation of Breast Cancer Biomarkers Identified by Mass Spectrometry: Some of the authors of the article cited above respond: Clin. Chem., April 1, 2006; 52(4): 772 - 772. [Full Text] [PDF]
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