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

BMC Cancer

Research Article

Bo AG Jönsson¹  Monica H Kåredal¹  Christian H Lindh¹  Marina C Jeppsson¹  Marie-Christine W Gast²  Jos H Beijnen³  Esmeralda JM Krop⁴  Diederick E Grobbee⁵  Carla H van Gils⁵  Petra HM Peeters⁶  Annemieke WJ Opstal-van Winden⁷  Roel CH Vermeulen⁸ 

[1] Department of Occupational and Environmental Medicine, Lund University, SE- 221 85, Lund, Sweden;Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066, Amsterdam, EC, The Netherlands;Central Hospital Pharmacy, Escamplaan 900, 2547, The Hague, EX, The Netherlands;Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066, Amsterdam, EC, The Netherlands;Faculty of Science, Department of Pharmaceutical Sciences, Division of Biomedical Analysis, Section of Drug Toxicology, Utrecht University, Sorbonnelaan 16, 3584, Utrecht, CA, The Netherlands;Institute for Risk Assessment Sciences, Utrecht University, Jenalaan 18D, 3584, Utrecht, CK, The Netherlands;Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584, Utrecht, CG, The Netherlands;Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584, Utrecht, CG, The Netherlands;Department of Epidemiology, Public Health and Primary Care, Faculty of Medicine, Imperial College Norfolk Place, W2 1PG, London, UK;Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584, Utrecht, CG, The Netherlands;Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066, Amsterdam, EC, The Netherlands;Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584, Utrecht, CG, The Netherlands;Institute for Risk Assessment Sciences, Utrecht University, Jenalaan 18D, 3584, Utrecht, CK, The Netherlands;

关键词: Biomarkers;    Breast cancer;    Early diagnosis;    2D-nanoLC-MS/MS;    Prospective;    Proteomics;    SELDI-TOF MS;   

DOI  :  10.1186/1471-2407-11-381

 received in 2011-04-27, accepted in 2011-08-26,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundSerum 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.MethodsIn 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).ResultsTwo 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.ConclusionsWe show that serum protein profiles are already altered up to three years before breast cancer detection.

【 授权许可】

Unknown   
© Opstal-van Winden et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.