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Proteomics and Protein Markers |
Departments of1
Pathology and 4
Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
2 National Cancer Institute of Milan, Milan, Italy.
3 University of Texas MD Anderson Cancer Center, Houston, TX.
5 Ciphergen Biosystems, Inc., Fremont, CA.
aAddress correspondence to this author at: Department of Pathology, Johns Hopkins Medical Institutions, 422 North Bond St., Baltimore, MD 21231. Fax 410-502-7882.
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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  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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 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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 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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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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