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[Cancer Research 62, 3609-3614, July 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Serum Protein Fingerprinting Coupled with a Pattern-matching Algorithm Distinguishes Prostate Cancer from Benign Prostate Hyperplasia and Healthy Men1

Bao-Ling Adam2, Yinsheng Qu2, John W. Davis, Michael D. Ward, Mary Ann Clements, Lisa H. Cazares, O. John Semmes, Paul F. Schellhammer, Yutaka Yasui, Ziding Feng and George L. Wright, Jr.2,,3

Departments of Microbiology and Molecular Cell Biology [B-L. A., M. D. W., M. A. C., L. H. C., O. J. S., G. L. W.] and Urology [P. F. S., G. L. W.] and Virginia Prostate Center [B-L. A., J. W. D., M. D. W., M. A. C., L. H. C., O. J. S., P. F. S., G. L. W.], Eastern Virginia Medical School, Norfolk, Virginia, 23501; Sentara Cancer Institute, Norfolk, Virginia 23501 [B-L. A., J. W. D., M. D. W., M. A. C., L. H. C., O. J. S., P. F. S., G. L. W.]; Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [J. W. D.]; and Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 [Y. Q., Y. Y., Z. F.]

The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better biomarkers for early detection of PCA using protein profiling technologies that can simultaneously resolve and analyze multiple proteins. Evaluating multiple proteins will be essential to establishing signature proteomic patterns that distinguish cancer from noncancer as well as identify all genetic subtypes of the cancer and their biological activity. In this study, we used a protein biochip surface enhanced laser desorption/ionization mass spectrometry approach coupled with an artificial intelligence learning algorithm to differentiate PCA from noncancer cohorts. Surface enhanced laser desorption/ionization mass spectrometry protein profiles of serum from 167 PCA patients, 77 patients with benign prostate hyperplasia, and 82 age-matched unaffected healthy men were used to train and develop a decision tree classification algorithm that used a nine-protein mass pattern that correctly classified 96% of the samples. A blinded test set, separated from the training set by a stratified random sampling before the analysis, was used to determine the sensitivity and specificity of the classification system. A sensitivity of 83%, a specificity of 97%, and a positive predictive value of 96% for the study population and 91% for the general population were obtained when comparing the PCA versus noncancer (benign prostate hyperplasia/healthy men) groups. This high-throughput proteomic classification system will provide a highly accurate and innovative approach for the early detection/diagnosis of PCA.




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Z. Xiao, B. T. Luke, G. Izmirlian, A. Umar, P. M. Lynch, R. K. S. Phillips, S. Patterson, T. P. Conrads, T. D. Veenstra, P. Greenwald, et al.
Serum Proteomic Profiles Suggest Celecoxib-Modulated Targets and Response Predictors
Cancer Res., April 15, 2004; 64(8): 2904 - 2909.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
D. F. Ransohoff
Virtual Colonoscopy--What It Can Do vs What It Will Do
JAMA, April 14, 2004; 291(14): 1772 - 1774.
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 Mol. Cell. ProteomicsHome page
I. J. Jacobs and U. Menon
Progress and Challenges in Screening for Early Detection of Ovarian Cancer
Mol. Cell. Proteomics, April 1, 2004; 3(4): 355 - 366.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. ProteomicsHome page
E. P. Diamandis
Mass Spectrometry as a Diagnostic and a Cancer Biomarker Discovery Tool: Opportunities and Potential Limitations
Mol. Cell. Proteomics, April 1, 2004; 3(4): 367 - 378.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
E. P. Diamandis
Analysis of Serum Proteomic Patterns for Early Cancer Diagnosis: Drawing Attention to Potential Problems
J Natl Cancer Inst, March 3, 2004; 96(5): 353 - 356.
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 Clin. Cancer Res.Home page
J. T. Wadsworth, K. D. Somers, L. H. Cazares, G. Malik, B.-L. Adam, B. C. Stack Jr., G. L. Wright Jr., and O. J. Semmes
Serum Protein Profiles to Identify Head and Neck Cancer
Clin. Cancer Res., March 1, 2004; 10(5): 1625 - 1632.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
D. H. Geho, E. F. Petricoin, and L. A. Liotta
Blasting into the Microworld of Tissue Proteomics: A New Window on Cancer: Commentary re S. A. Schwartz et al., Protein Profiling in Brain Tumors Using Mass Spectrometry: Feasibility of a New Technique for the Analysis of Protein Expression. Clin. Cancer Res., 10: 981-987, 2004.
Clin. Cancer Res., February 1, 2004; 10(3): 825 - 827.
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 Clin. Cancer Res.Home page
J. Koopmann, Z. Zhang, N. White, J. Rosenzweig, N. Fedarko, S. Jagannath, M. I. Canto, C. J. Yeo, D. W. Chan, and M. Goggins
Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry
Clin. Cancer Res., February 1, 2004; 10(3): 860 - 868.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. B. Martin, D. R. Gifford, M. E. Wright, A. Keller, E. Yi, D. R. Goodlett, R. Aebersold, and P. S. Nelson
Quantitative Proteomic Analysis of Proteins Released by Neoplastic Prostate Epithelium
Cancer Res., January 1, 2004; 64(1): 347 - 355.
[Abstract] [Full Text] [PDF]

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 Arch Otolaryngol Head Neck SurgHome page
J. T. Wadsworth, K. D. Somers, B. C. Stack Jr, L. Cazares, G. Malik, B.-L. Adam, G. L. Wright Jr, and O. J. Semmes
Identification of Patients With Head and Neck Cancer Using Serum Protein Profiles
Arch Otolaryngol Head Neck Surg, January 1, 2004; 130(1): 98 - 104.
[Abstract] [Full Text] [PDF]

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 Toxicol PatholHome page
E. F. Petricoin, V. Rajapaske, E. H. Herman, A. M. Arekani, S. Ross, D. Johann, A. Knapton, J. Zhang, B. A. Hitt, T. P. Conrads, et al.
Toxicoproteomics: Serum Proteomic Pattern Diagnostics for Early Detection of Drug Induced Cardiac Toxicities and Cardioprotection
Toxicol Pathol, January 1, 2004; 32(1_suppl): 122 - 130.
[Abstract] [PDF]

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 JNCI J Natl Cancer InstHome page
D. Sidransky, R. Irizarry, J. A. Califano, X. Li, H. Ren, N. Benoit, and L. Mao
Serum Protein MALDI Profiling to Distinguish Upper Aerodigestive Tract Cancer Patients From Control Subjects
J Natl Cancer Inst, November 19, 2003; 95(22): 1711 - 1717.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. A. Rogers, P. Clarke, J. Noble, N. P. Munro, A. Paul, P. J. Selby, and R. E. Banks
Proteomic Profiling of Urinary Proteins in Renal Cancer by Surface Enhanced Laser Desorption Ionization and Neural-Network Analysis: Identification of Key Issues Affecting Potential Clinical Utility
Cancer Res., October 15, 2003; 63(20): 6971 - 6983.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
E. P. Diamandis
Proteomic Patterns in Biological Fluids: Do They Represent the Future of Cancer Diagnostics?
Clin. Chem., August 1, 2003; 49(8): 1272 - 1275.
[Full Text] [PDF]

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 Clin. Chem.Home page
E. Petricoin III and L. A. Liotta
The Vision for a New Diagnostic Paradigm
Clin. Chem., August 1, 2003; 49(8): 1276 - 1278.
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 Cancer Res.Home page
P. Stattin, M. Hakama, G. L. Wright Jr., and P. F. Schellhammer
Correspondence re: B-L. Adam et al., Serum Protein Fingerprinting Coupled with a Pattern-matching Algorithm Distinguishes Prostate Cancer from Benign Prostate Hyperplasia and Healthy Men. Cancer Res., 62: 3609-3614, 2002
Cancer Res., May 15, 2003; 63(10): 2701 - 2702.
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 JNCI J Natl Cancer InstHome page
D. R. Rhodes, M. G. Sanda, A. P. Otte, A. M. Chinnaiyan, and M. A. Rubin
Multiplex Biomarker Approach for Determining Risk of Prostate-Specific Antigen-Defined Recurrence of Prostate Cancer
J Natl Cancer Inst, May 7, 2003; 95(9): 661 - 668.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
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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 Clin. Chem.Home page
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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 Clin. Cancer Res.Home page
B. J. Duggan, J. J. McKnight, K. E. Williamson, M. Loughrey, D. O'Rourke, P. W. Hamilton, S. R. Johnston, C. C. Schulman, and A. R. Zlotta
The Need to Embrace Molecular Profiling of Tumor Cells in Prostate and Bladder Cancer
Clin. Cancer Res., April 1, 2003; 9(4): 1240 - 1247.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
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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 Clin. Chem.Home page
Y. Qu, B.-L. Adam, Y. Yasui, M. D. Ward, L. H. Cazares, P. F. Schellhammer, Z. Feng, O. J. Semmes, and G. L. Wright Jr.
Boosted Decision Tree Analysis of Surface-enhanced Laser Desorption/Ionization Mass Spectral Serum Profiles Discriminates Prostate Cancer from Noncancer Patients
Clin. Chem., October 1, 2002; 48(10): 1835 - 1843.
[Abstract] [Full Text] [PDF]


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