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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study

Authors: Annemieke WJ Opstal-van Winden, Esmeralda JM Krop, Monica H Kåredal, Marie-Christine W Gast, Christian H Lindh, Marina C Jeppsson, Bo AG Jönsson, Diederick E Grobbee, Petra HM Peeters, Jos H Beijnen, Carla H van Gils, Roel CH Vermeulen

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort.

Methods

In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS).

Results

Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3adesArg and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.

Conclusions

We show that serum protein profiles are already altered up to three years before breast cancer detection.
Appendix
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Literature
1.
Lord SJ, Lei W, Craft P, Cawson JN, Morris I, Walleser S, Griffiths A, Parker S, Houssami N: A systematic review of the effectiveness of magnetic resonance imaging (MRI) as an addition to mammography and ultrasound in screening young women at high risk of breast cancer. Eur J Cancer. 2007, 43: 1905-1917. 10.1016/j.ejca.2007.06.007.CrossRefPubMed
2.
Hu Y, Zhang S, Yu J, Liu J, Zheng S: SELDI-TOF-MS: the proteomics and bioinformatics approaches in the diagnosis of breast cancer. Breast. 2005, 14: 250-255. 10.1016/j.breast.2005.01.008.CrossRefPubMed
3.
Belluco C, Petricoin EF, Mammano E, Facchiano F, Ross-Rucker S, Nitti D, Maggio CD, Liu C, Lise M, Liotta LA, Whiteley G: Serum proteomic analysis identifies a highly sensitive and specific discriminatory pattern in stage 1 breast cancer. Ann Surg Oncol. 2007, 14: 2470-2476. 10.1245/s10434-007-9354-3.CrossRefPubMed
4.
Vlahou A, Laronga C, Wilson L, Gregory B, Fournier K, McGaughey D, Perry RR, Wright GL, Semmes OJ: A novel approach toward development of a rapid blood test for breast cancer. Clin Breast Cancer. 2003, 4: 203-209. 10.3816/CBC.2003.n.026.CrossRefPubMed
5.
Gast MC, Bonfrer JM, van Dulken EJ, de Kock L, Rutgers EJ, Schellens JH, Beijnen JH: SELDI-TOF MS serum protein profiles in breast cancer: assessment of robustness and validity. Cancer Biomark. 2006, 2: 235-248.PubMed
6.
Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW: Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin Chem. 2002, 48: 1296-1304.PubMed
7.
Li J, Orlandi R, White CN, Rosenzweig J, Zhao J, Seregni E, Morelli D, Yu Y, Meng XY, Zhang Z, Davidson NE, Fung ET, et al: Independent validation of candidate breast cancer serum biomarkers identified by mass spectrometry. Clin Chem. 2005, 51: 2229-2235. 10.1373/clinchem.2005.052878.CrossRefPubMed
8.
Mathelin C, Cromer A, Wendling C, Tomasetto C, Rio MC: Serum biomarkers for detection of breast cancers: a prospective study. Breast Cancer Res Treat. 2006, 96: 83-90. 10.1007/s10549-005-9046-2.CrossRefPubMed
9.
van Winden AW, Gast MC, Beijnen JH, Rutgers EJ, Grobbee DE, Peeters PH, van Gils CH: Validation of previously identified serum biomarkers for breast cancer with SELDI-TOF MS: a case control study. BMC Med Genomics. 2009, 2: 4-10.1186/1755-8794-2-4.CrossRefPubMedPubMedCentral
10.
Hsieh SY, Chen RK, Pan YH, Lee HL: Systematical evaluation of the effects of sample collection procedures on low-molecular-weight serum/plasma proteome profiling. Proteomics. 2006, 6: 3189-3198. 10.1002/pmic.200500535.CrossRefPubMed
11.
Timms JF, Arslan-Low E, Gentry-Maharaj A, Luo Z, T'Jampens D, Podust VN, Ford J, Fung ET, Gammerman A, Jacobs I, Menon U: Preanalytic influence of sample handling on SELDI-TOF serum protein profiles. Clin Chem. 2007, 53: 645-656. 10.1373/clinchem.2006.080101.CrossRefPubMed
12.
Villanueva J, Philip J, Chaparro CA, Li Y, Toledo-Crow R, DeNoyer L, Fleisher M, Robbins RJ, Tempst P: Correcting common errors in identifying cancer-specific serum peptide signatures. J Proteome Res. 2005, 4: 1060-1072. 10.1021/pr050034b.CrossRefPubMedPubMedCentral
13.
West-Nielsen M, Hogdall EV, Marchiori E, Hogdall CK, Schou C, Heegaard NH: Sample handling for mass spectrometric proteomic investigations of human sera. Anal Chem. 2005, 77: 5114-5123. 10.1021/ac050253g.CrossRefPubMed
14.
Banks RE, Stanley AJ, Cairns DA, Barrett JH, Clarke P, Thompson D, Selby PJ: Influences of blood sample processing on low-molecular-weight proteome identified by surface-enhanced laser desorption/ionization mass spectrometry. Clin Chem. 2005, 51: 1637-1649. 10.1373/clinchem.2005.051417.CrossRefPubMed
15.
Engwegen JY, Alberts M, Knol JC, Jimenez CR, Depla AC, Tuynman H, Snel P, Smits ME, Cats A, Schellens JH, Beijnen JH: Influence of variations in sample handling on SELDI-TOF MS serum protein profiles for colorectal cancer. Proteomics Clin Appl. 2008, 2: 936-945. 10.1002/prca.200780068.CrossRefPubMed
16.
Karsan A, Eigl BJ, Flibotte S, Gelmon K, Switzer P, Hassell P, Harrison D, Law J, Hayes M, Stillwell M, Xiao Z, Conrads TP, et al: Analytical and preanalytical biases in serum proteomic pattern analysis for breast cancer diagnosis. Clin Chem. 2005, 51: 1525-1528. 10.1373/clinchem.2005.050708.CrossRefPubMed
17.
Pitteri SJ, Amon LM, Busald BT, Zhang Y, Johnson MM, Chin A, Kennedy J, Wong CH, Zhang Q, Wang H, Lampe PD, Prentice RL, et al: Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users. Cancer Res. 2010, 70: 8598-8606. 10.1158/0008-5472.CAN-10-1676.CrossRefPubMedPubMedCentral
18.
Boker LK, van Noord PA, van der Schouw YT, Koot NV, Bueno de Mesquita HB, Riboli E, Grobbee DE, Peeters PH: Prospect-EPIC Utrecht: study design and characteristics of the cohort population. European Prospective Investigation into Cancer and Nutrition. Eur J Epidemiol. 2001, 17: 1047-1053. 10.1023/A:1020009325797.CrossRefPubMed
19.
Pols MA, Peeters PH, Ocke MC, Slimani N, Bueno-de-Mesquita HB, Collette HJ: Estimation of reproducibility and relative validity of the questions included in the EPIC Physical Activity Questionnaire. Int J Epidemiol. 1997, 26 (Suppl 1): S181-S189.CrossRefPubMed
20.
Pitteri SJ, Hanash SM: Confounding effects of hormone replacement therapy in protein biomarker studies. Cancer Epidemiol Biomarkers Prev. 2011, 20: 134-139. 10.1158/1055-9965.EPI-10-0673.CrossRefPubMed
21.
Hu J, Coombes KR, Morris JS, Baggerly KA: The importance of experimental design in proteomic mass spectrometry experiments: some cautionary tales. Brief Funct Genomic Proteomic. 2005, 3: 322-331. 10.1093/bfgp/3.4.322.CrossRefPubMed
22.
Pelikan R, Bigbee WL, Malehorn D, Lyons-Weiler J, Hauskrecht M: Intersession reproducibility of mass spectrometry profiles and its effect on accuracy of multivariate classification models. Bioinformatics. 2007, 23: 3065-3072. 10.1093/bioinformatics/btm415.CrossRefPubMed
23.
Gast MC, van Gils CH, Wessels LF, Harris N, Bonfrer JM, Rutgers EJ, Schellens JH, Beijnen JH: Serum protein profiling for diagnosis of breast cancer using SELDI-TOF MS. Oncol Rep. 2009, 22: 205-213.CrossRefPubMed
24.
Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statistic Soc B. 1995, 57: 289-300.
25.
Kersey PJ, Duarte J, Williams A, Karavidopoulou Y, Birney E, Apweiler R: The International Protein Index: an integrated database for proteomics experiments. Proteomics. 2004, 4: 1985-1988. 10.1002/pmic.200300721.CrossRefPubMed
26.
Engwegen JY, Helgason HH, Cats A, Harris N, Bonfrer JM, Schellens JH, Beijnen JH: Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry. World J Gastroenterol. 2006, 12: 1536-1544.CrossRefPubMedPubMedCentral
27.
Gast MC, van Gils CH, Wessels LF, Harris N, Bonfrer JM, Rutgers EJ, Schellens JH, Beijnen JH: Influence of sample storage duration on serum protein profiles assessed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS). Clin Chem Lab Med. 2009, 47: 694-705. 10.1515/CCLM.2009.151.CrossRefPubMed
28.
Goncalves A, Esterni B, Bertucci F, Sauvan R, Chabannon C, Cubizolles M, Bardou VJ, Houvenaegel G, Jacquemier J, Granjeaud S, Meng XY, Fung ET, et al: Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy. Oncogene. 2006, 25: 981-989. 10.1038/sj.onc.1209131.CrossRefPubMed
29.
Villanueva J, Shaffer DR, Philip J, Chaparro CA, Erdjument-Bromage H, Olshen AB, Fleisher M, Lilja H, Brogi E, Boyd J, Sanchez-Carbayo M, Holland EC, et al: Differential exoprotease activities confer tumor-specific serum peptidome patterns. J Clin Invest. 2006, 116: 271-284.CrossRefPubMedPubMedCentral
30.
Song J, Patel M, Rosenzweig CN, Chan-Li Y, Sokoll LJ, Fung ET, Choi-Miura NH, Goggins M, Chan DW, Zhang Z: Quantification of fragments of human serum inter-alpha-trypsin inhibitor heavy chain 4 by a surface-enhanced laser desorption/ionization-based immunoassay. Clin Chem. 2006, 52: 1045-1053. 10.1373/clinchem.2005.065722.CrossRefPubMed
31.
van Winden AW, van den Broek I, Gast MC, Engwegen JY, Sparidans RW, Dulken EJ, Depla AC, Cats A, Schellens JH, Peeters PH, Beijnen JH, van Gils CH: Serum degradome markers for the detection of breast cancer. J Proteome Res. 2010, 9: 3781-3788. 10.1021/pr100395s.CrossRefPubMed
32.
Kreienberg R, Koehler P, Kasemeyer R, Melchert F: Clinical utility of different tumor markers in breast cancer and gynecological malignancies. Cancer Detect Prev. 1983, 6: 221-225.PubMed
33.
Lamoureux G, Mandeville R, Poisson R, Legault-Poisson S, Jolicoeur R: Biologic markers and breast cancer: a multiparametric study--1. Increased serum protein levels. Cancer. 1982, 49: 502-512. 10.1002/1097-0142(19820201)49:3<502::AID-CNCR2820490318>3.0.CO;2-D.CrossRefPubMed
34.
Hutchens TW, Yip TT: New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Commun Mass Spectrom. 1993, 7: 576-580. 10.1002/rcm.1290070703.CrossRef
35.
Merchant M, Weinberger SR: Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. Electrophoresis. 2000, 21: 1164-1177. 10.1002/(SICI)1522-2683(20000401)21:6<1164::AID-ELPS1164>3.0.CO;2-0.CrossRefPubMed
36.
Lee SM, Hwang KS, Yoon HJ, Yoon DS, Kim SK, Lee YS, Kim TS: Sensitivity enhancement of a dynamic mode microcantilever by stress inducer and mass inducer to detect PSA at low picogram levels. Lab Chip. 2009, 9: 2683-2690. 10.1039/b902922b.CrossRefPubMed
Metadata
Title
Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
Authors
Annemieke WJ Opstal-van Winden
Esmeralda JM Krop
Monica H Kåredal
Marie-Christine W Gast
Christian H Lindh
Marina C Jeppsson
Bo AG Jönsson
Diederick E Grobbee
Petra HM Peeters
Jos H Beijnen
Carla H van Gils
Roel CH Vermeulen
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-381

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