Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis
Tóm tắt
Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response. Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance. Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified. Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.
Tài liệu tham khảo
Society, AC Cancer Facts and Figures 2004. Atlanta, GA. 2004
Omenn GS: Human lung cancer chemoprevention strategies: Parker B. Francis Lecture. Chest. 2004, 125 (5 Suppl): 123S-127S. 10.1378/chest.125.5_suppl.123S.
Carbone DP: The biology of lung cancer. Semin Oncol. 1997, 24 (4): 388-401.
Xiao X, Liu D, Tang Y, Guo F, Xia L, Liu J, He D: Development of proteomic patterns for detecting lung cancer. Dis Markers. 2003, 19 (1): 33-39.
Zhukov TA, Johanson RA, Cantor AB, Clark RA, Tockman MS: Discovery of distinct protein profiles specific for lung tumors and pre-malignant lung lesions by SELDI mass spectrometry. Lung Cancer. 2003, 40 (3): 267-279.
Knezevic V, Leethanakul C, Bichsel VE, Worth JM, Prabhu VV, Gutkind JS, Liotta LA, Munson PJ, Petricoin EF, Krizman DB: Proteomic profiling of the cancer microenvironment by antibody arrays. Proteomics. 2001, 1 (10): 1271-1278. 10.1002/1615-9861(200110)1:10<1271::AID-PROT1271>3.3.CO;2-Y.
Sreekumar A, Nyati MK, Varambally S, Barrette TR, Ghosh D, Lawrence TS, Chinnaiyan AM: Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 2001, 61 (20): 7585-7593.
Joos TO, Schrenk M, Hopfl P, Kroger K, Chowdhury U, Stoll D, Schorner D, Durr M, Herick K, Rupp S, Sohn K, Hammerle H: A microarray enzyme-linked immunosorbent assay for autoimmune diagnostics. Electrophoresis. 2000, 21 (13): 2641-2650. 10.1002/1522-2683(20000701)21:13<2641::AID-ELPS2641>3.0.CO;2-5.
MacBeath G, Schreiber SL: Printing proteins as microarrays for high-throughput function determination. Science. 2000, 289 (5485): 1760-1763.
Ge H: UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions. Nucleic Acids Res. 2000, 28 (2): e3-10.1093/nar/28.2.e3.
Lueking A, Horn M, Eickhoff H, Bussow K, Lehrach H, Walter G: Protein microarrays for gene expression and antibody screening. Anal Biochem. 1999, 270 (1): 103-111. 10.1006/abio.1999.4063.
Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P, Lan N, Jansen R, Bidlingmaier S, Houfek T, Mitchell T, Miller P, Dean RA, Gerstein M, Snyder M: Global analysis of protein activities using proteome chips. Science. 2001, 293 (5537): 2101-2105. 10.1126/science.1062191.
Haab BB, Dunham MJ, Brown PO: Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Genome Biol. 2001, 2 (2): RESEARCH0004-10.1186/gb-2001-2-2-research0004.
Mendoza LG, McQuary P, Mongan A, Gangadharan R, Brignac S, Eggers M: High-throughput microarray-based enzyme-linked immunosorbent assay (ELISA). Biotechniques. 1999, 27 (4): 778-780. 782–776,788.
de Wildt RM, Mundy CR, Gorick BD, Tomlinson IM: Antibody arrays for high-throughput screening of antibody-antigen interactions. Nat Biotechnol. 2000, 18 (9): 989-994. 10.1038/79494.
Arenkov P, Kukhtin A, Gemmell A, Voloshchuk S, Chupeeva V, Mirzabekov A: Protein microchips: use for immunoassay and enzymatic reactions. Anal Biochem. 2000, 278 (2): 123-131. 10.1006/abio.1999.4363.
Huang RP, Huang R, Fan Y, Lin Y: Simultaneous detection of multiple cytokines from conditioned media and patient's sera by an antibody-based protein array system. Anal Biochem. 2001, 294 (1): 55-62. 10.1006/abio.2001.5156.
Haab BB: Methods and applications of antibody microarrays in cancer research. Proteomics. 2003, 3 (11): 2116-2122. 10.1002/pmic.200300595.
Haab BB, Zhou H: Multiplexed protein analysis using spotted antibody microarrays. Methods Mol Biol. 2004, 264: 33-45.
Zhou H, Bouwman K, Schotanus M, Verweij C, Marrero JA, Dillon D, Costa J, Lizardi P, Haab BB: Two-color, rolling-circle amplification on antibody microarrays for sensitive, multiplexed serum-protein measurements. Genome Biol. 2004, 5 (4): R28-10.1186/gb-2004-5-4-r28.
Schweitzer B, Wiltshire S, Lambert J, O'Malley S, Kukanskis K, Zhu Z, Kingsmore SF, Lizardi PM, Ward DC: Inaugural article: immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection. Proc Natl Acad Sci U S A. 2000, 97 (18): 10113-10119. 10.1073/pnas.170237197.
Detailed antibody, patient serum and experimental information. [http://dot.ped.med.umich.edu:2000/pub/AbMicro/index.htm]
Miller JC, Zhou H, Kwekel J, Cavallo R, Burke J, Butler EB, Teh BS, Haab BB: Antibody microarray profiling of human prostate cancer sera: antibody screening and identification of potential biomarkers. Proteomics. 2003, 3 (1): 56-63. 10.1002/pmic.200390009.
Dudoit S, Fridlyand J, Speed TP: Comparison of discrimination methods for the classification of tumors using gene expression data. Journal of the American Statistical Association. 2002, 97: 77-87. 10.1198/016214502753479248.
Pepys MB, Hirschfield GM: C-reactive protein: a critical update. J Clin Invest. 2003, 111 (12): 1805-1812. 10.1172/JCI200318921.
Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V: C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004, 350 (14): 1387-1397. 10.1056/NEJMoa032804.
Tall AR: C-reactive protein reassessed. N Engl J Med. 2004, 350 (14): 1450-1452. 10.1056/NEJMe048020.
McKeown DJ, Brown DJ, Kelly A, Wallace AM, McMillan DC: The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. Brit J Cancer. 2004, 91: 1993-1995. 10.1038/sj.bjc.6602248.
Scott HR, McMillan DC, Crilly A, McArdle CS, Milroy R: The relationship between weight loss and interleukin 6 in non-small-cell lung cancer. Brit J Cancer. 1996, 73 (12): 1560-1562.
Nozoe T, Saeki H, Sugimachi K: Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg. 2001, 182 (2): 197-201. 10.1016/S0002-9610(01)00684-5.
Kato K, Hitsuda Y, Kawasaki Y, Igishi T, Yasuda K, Mikami M, Watanabe M, Miyata M, Sasaki T, Shimizu E: [The value of serum C-reactive protein as a survival determinant in patients with advanced non-small-cell lung cancer]. Nihon Kokyuki Gakkai Zasshi. 2000, 38 (8): 575-580.
Arpin D, Trillet-Lenoir V, Lasset C, Souquet PJ, Riou R, Yoanidis I, Guidollet J, Cordier JF, Brune J: [Value of C-reactive protein determination in small cell lung cancer]. Bull Cancer. 1993, 80 (12): 1063-1068.
Raynes JG, Eagling S, McAdam KP: Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6. Clin Exp Immunol. 1991, 83 (3): 488-491.
Bausserman LL, Herbert PN, Rodger R, Nicolosi RJ: Rapid clearance of serum amyloid A from high-density lipoproteins. Biochim Biophys Acta. 1984, 792 (2): 186-191.
d'Eril GM, Anesi A, Maggiore M, Leoni V: Biological variation of serum amyloid A in healthy subjects. Clin Chem. 2001, 47 (8): 1498-1499.
Biran H, Friedman N, Neumann L, Pras M, Shainkin-Kestenbaum R: Serum amyloid A (SAA) variations in patients with cancer: correlation with disease activity, stage, primary site, and prognosis. J Clin Pathol. 1986, 39 (7): 794-797.
Kimura M, Tomita Y, Imai T, Saito T, Katagiri A, Ohara-Mikami Y, Matsudo T, Takahashi K: Significance of serum amyloid A on the prognosis in patients with renal cell carcinoma. Cancer. 2001, 92 (8): 2072-2075. 10.1002/1097-0142(20011015)92:8<2072::AID-CNCR1547>3.0.CO;2-P.
Glojnaric I, Casl MT, Simic D, Lukac J: Serum amyloid A protein (SAA) in colorectal carcinoma. Clin Chem Lab Med. 2001, 39 (2): 129-133. 10.1515/CCLM.2001.022.
Kaneti J, Winikoff Y, Zimlichman S, Shainkin-Kestenbaum R: Importance of serum amyloid A (SAA) level in monitoring disease activity and response to therapy in patients with prostate cancer. Urol Res. 1984, 12 (5): 239-241. 10.1007/BF00256147.
Cho WC, Yip TT, Yip C, Yip V, Thulasiraman V, Ngan RK, Yip TT, Lau WH, Au JS, Law SC, Cheng WW, Ma VW, Lim CK: Identification of serum amyloid a protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling. Clin Cancer Res. 2004, 10 (1 Pt 1): 43-52.
Benson MD, Cohen AS: Serum amyloid A protein in amyloidosis, rheumatic, and enoplastic diseases. Arthritis Rheum. 1979, 22 (1): 36-42.
Rosenthal CJ, Sullivan LM: Serum amyloid A to monitor cancer dissemination. Ann Intern Med. 1979, 91 (3): 383-390.
Crystal RG: The alpha 1-antitrypsin gene and its deficiency states. Trends Genet. 1989, 5 (12): 411-417. 10.1016/0168-9525(89)90200-X.
Sun Z, Yang P: Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression. Lancet Oncol. 2004, 5 (3): 182-190. 10.1016/S1470-2045(04)01414-7.
Homolka J, Voslarova Z, Malbohan I: [Significance of alpha-1-antitrypsin and alpha-2-pregnancy-associated glycoprotein in the serum of patients with bronchial carcinoma]. Z Erkr Atmungsorgane. 1987, 169 (1): 38-43.
Di Martino G, Iannucci F, Bizzarro A, Iacono G: [Association of serum tumor markers in solid neoplasms (CEA, ferritin, alpha 1-antitrypsin, parathormone and calcitonin)]. Boll Ist Sieroter Milan. 1982, 61 (5): 411-422.
Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R: An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis. Br J Cancer. 1992, 65 (2): 300-302.
Weinstein PS, Skinner M, Sipe JD, Lokich JJ, Zamcheck N, Cohen AS: Acute-phase proteins or tumour markers: the role of SAA, SAP, CRP and CEA as indicators of metastasis in a broad spectrum of neoplastic diseases. Scand J Immunol. 1984, 19 (3): 193-198.
Gendler SJ, Spicer AP: Epithelial mucin genes. Annu Rev Physiol. 1995, 57: 607-634. 10.1146/annurev.ph.57.030195.003135.
Wesseling J, van der Valk SW, Hilkens J: A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1. Mol Biol Cell. 1996, 7 (4): 565-577.
Wesseling J, van der Valk SW, Vos HL, Sonnenberg A, Hilkens J: Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol. 1995, 129 (1): 255-265. 10.1083/jcb.129.1.255.
Wolman SR, Pauley RJ, Mohamed AN, Dawson PJ, Visscher DW, Sarkar FH: Genetic markers as prognostic indicators in breast cancer. Cancer. 1992, 70 (6 Suppl): 1765-1774.
Sasaki M, Nakanuma Y, Shimizu K, Izumi R: Pathological and immunohistochemical findings in a case of mucinous cholangiocarcinoma. Pathol Int. 1995, 45 (10): 781-786.
Ajioka Y, Allison LJ, Jass JR: Significance of MUC1 and MUC2 mucin expression in colorectal cancer. J Clin Pathol. 1996, 49 (7): 560-564.
McGuckin MA, Walsh MD, Hohn BG, Ward BG, Wright RG: Prognostic significance of MUC1 epithelial mucin expression in breast cancer. Hum Pathol. 1995, 26 (4): 432-439. 10.1016/0046-8177(95)90146-9.
Nakamori S, Ota DM, Cleary KR, Shirotani K, Irimura T: MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology. 1994, 106 (2): 353-361.
Gendler SJ, Lancaster CA, Taylor-Papadimitriou J, Duhig T, Peat N, Burchell J, Pemberton L, Lalani EN, Wilson D: Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem. 1990, 265 (25): 15286-15293.
Ohgami A, Tsuda T, Osaki T, Mitsudomi T, Morimoto Y, Higashi T, Yasumoto K: MUC1 mucin mRNA expression in stage I lung adenocarcinoma and its association with early recurrence. Ann Thorac Surg. 1999, 67 (3): 810-814. 10.1016/S0003-4975(99)00041-7.
Nguyen PL, Niehans GA, Cherwitz DL, Kim YS, Ho SB: Membrane-bound (MUC1) and secretory (MUC2, MUC3, and MUC4) mucin gene expression in human lung cancer. Tumour Biol. 1996, 17 (3): 176-192.
Guddo F, Giatromanolaki A, Koukourakis MI, Reina C, Vignola AM, Chlouverakis G, Hilkens J, Gatter KC, Harris AL, Bonsignore G: MUC1 (episialin) expression in non-small cell lung cancer is independent of EGFR and c-erbB-2 expression and correlates with poor survival in node positive patients. J Clin Pathol. 1998, 51 (9): 667-671.
Ho SB, Niehans GA, Lyftogt C, Yan PS, Cherwitz DL, Gum ET, Dahiya R, Kim YS: Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res. 1993, 53 (3): 641-651.
Devine PL, McGuckin MA, Ramm LE, Ward BG, Pee D, Long S: Serum mucin antigens CASA and MSA in tumors of the breast, ovary, lung, pancreas, bladder, colon, and prostate. A blind trial with 420 patients. Cancer. 1993, 72 (6): 2007-2015.
Hayes DF, Sekine H, Ohno T, Abe M, Keefe K, Kufe DW: Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients. J Clin Invest. 1985, 75 (5): 1671-1678.
Croce MV, Isla-Larrain MT, Demichelis SO, Gori JR, Price MR, Segal-Eiras A: Tissue and serum MUC1 mucin detection in breast cancer patients. Breast Cancer Res Treat. 2003, 81 (3): 195-207. 10.1023/A:1026110417294.
Cannon PM, Ellis IO, Blamey RW, Bell J, Elston CW, Robertson JF: Expression of tumour-associated antigens in breast cancer primary tissue compared with serum levels. Eur J Surg Oncol. 1993, 19 (6): 523-527.
Ahmed N, Barker G, Oliva KT, Hoffmann P, Riley C, Reeve S, Smith AI, Kemp BE, Quinn MA, Rice GE: Proteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer. Brit J Cancer. 2004, 91: 129-140. 10.1038/sj.bjc.6601882.
Ye B, Cramer DW, Skates SJ, Gygi SP, Pratomo V, Fu L, Horick NK, Licklider LJ, Schorge JO, Berkowitz RS, Mok SC: Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry. Clin Cancer Res. 2003, 9: 2904-2911.
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