This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koomen, J. M. Articles by Kobayashi, R. Search for Related Content PubMed PubMed Citation Articles by Koomen, J. M. Articles by Kobayashi, R.

Plasma Protein Profiling for Diagnosis of Pancreatic Cancer Reveals the Presence of Host Response Proteins

Departments of ¹ Molecular Pathology, ² Cancer Biology, ³ Biostatistics and Applied Mathematics, and ⁴ Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Ryuji Kobayashi, Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-745-3363; Fax: 713-794-1294; E-mail: rkobayas{at}mail.mdanderson.org.

Plasma protein profiling using separations coupled to matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has great potential in translational research; it can be used for biomarker discovery and contribute to disease diagnosis and therapy. Previously reported biomarker searches have been done solely by MS protein profiling followed by bioinformatics analysis of the data. To add to current methods, we tested an alternative strategy for plasma protein profiling using pancreatic cancer as the model. First, offline solid-phase extraction is done with 96-well plates to fractionate and partially purify the proteins. Then, multiple profiling and identification experiments can be conducted on the same protein fractions because only 5% of the fractions are used for MALDI MS profiling. After MALDI MS analysis, the mass spectra are normalized and subjected to a peak detection algorithm. Over three sets of mass spectra acquired using different instrument variables, 400 unique ion signals were detected. Classification schemes employing as many as eight individual peaks were developed using a training set with 123 members (82 cancer patients) and a blinded validation set with 125 members (57 cancer patients). The sensitivity of the study was 88%, but the specificity was significantly lower, 75%. The reason for the low specificity becomes apparent upon protein identification of the ion signals used for the classification. The identifications reveal only common serum proteins and components of the acute phase response, including serum amyloid A, -1-antitrypsin, -1-antichymotrypsin, and inter--trypsin inhibitor.

Key Words: Protein Profiling • MALDI Mass Spectrometry • Pancreatic Cancer

This article has been cited by other articles:

				A. Gammerman, V. Vovk, B. Burford, I. Nouretdinov, Z. Luo, A. Chervonenkis, M. Waterfield, R. Cramer, P. Tempst, J. Villanueva, et al. Serum Proteomic Abnormality Predating Screen Detection of Ovarian Cancer The Computer Journal, April 15, 2008; (2008) bxn021v3. [Abstract] [Full Text] [PDF]

				Y. Tang, K. Kitisin, W. Jogunoori, C. Li, C.-X. Deng, S. C. Mueller, H. W. Ressom, A. Rashid, A. R. He, J. S. Mendelson, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-{beta} and IL-6 signaling PNAS, February 19, 2008; 105(7): 2445 - 2450. [Abstract] [Full Text] [PDF]

				A. Keller, N. Comtesse, N. Ludwig, E. Meese, and H.-P. Lenhof SePaCS--a web-based application for classification of seroreactivity profiles Nucleic Acids Res., July 13, 2007; 35(suppl_2): W683 - W687. [Abstract] [Full Text] [PDF]

				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]

				Y. V. Karpievitch, E. G. Hill, A. J. Smolka, J. S. Morris, K. R. Coombes, K. A. Baggerly, and J. S. Almeida PrepMS: TOF MS data graphical preprocessing tool Bioinformatics, January 15, 2007; 23(2): 264 - 265. [Abstract] [Full Text] [PDF]

				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]

				J. Song, M. Patel, C. N. Rosenzweig, Y. Chan-Li, L. J. Sokoll, E. T. Fung, N.-H. Choi-Miura, M. Goggins, D. W. Chan, and Z. Zhang Quantification of Fragments of Human Serum Inter-{alpha}-Trypsin Inhibitor Heavy Chain 4 by a Surface-Enhanced Laser Desorption/Ionization-Based Immunoassay Clin. Chem., June 1, 2006; 52(6): 1045 - 1053. [Abstract] [Full Text] [PDF]

				B. Ye, S. Skates, S. C. Mok, N. K. Horick, H. F. Rosenberg, A. Vitonis, D. Edwards, P. Sluss, W. K. Han, R. S. Berkowitz, et al. Proteomic-Based Discovery and Characterization of Glycosylated Eosinophil-Derived Neurotoxin and COOH-Terminal Osteopontin Fragments for Ovarian Cancer in Urine Clin. Cancer Res., January 15, 2006; 12(2): 432 - 441. [Abstract] [Full Text] [PDF]

				M. W. Duncan and S. W. Hunsucker Proteomics as a Tool for Clinically Relevant Biomarker Discovery and Validation Experimental Biology and Medicine, December 1, 2005; 230(11): 808 - 817. [Abstract] [Full Text] [PDF]

				K. Honda, Y. Hayashida, T. Umaki, T. Okusaka, T. Kosuge, S. Kikuchi, M. Endo, A. Tsuchida, T. Aoki, T. Itoi, et al. Possible Detection of Pancreatic Cancer by Plasma Protein Profiling Cancer Res., November 15, 2005; 65(22): 10613 - 10622. [Abstract] [Full Text] [PDF]

				H. W. Ressom, R. S. Varghese, M. Abdel-Hamid, S. A.-L. Eissa, D. Saha, L. Goldman, E. F. Petricoin, T. P. Conrads, T. D. Veenstra, C. A. Loffredo, et al. Analysis of mass spectral serum profiles for biomarker selection Bioinformatics, November 1, 2005; 21(21): 4039 - 4045. [Abstract] [Full Text] [PDF]

				M. Goggins Molecular Markers of Early Pancreatic Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4524 - 4531. [Abstract] [Full Text] [PDF]