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

<p>Abstract</p> <p>Background</p> <p>Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected <it>at </it>or <it>after </it>diagnosis. This ma...

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Main Authors: Peeters Petra HM, Grobbee Diederick E, Jönsson Bo AG, Jeppsson Marina C, Lindh Christian H, Gast Marie-Christine W, Kåredal Monica H, Krop Esmeralda JM, Opstal-van Winden Annemieke WJ, Beijnen Jos H, van Gils Carla H, Vermeulen Roel CH
Format: Article
Language:English
Published: BMC 2011-08-01
Series:BMC Cancer
Subjects:
Online Access:http://www.biomedcentral.com/1471-2407/11/381
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author Peeters Petra HM
Grobbee Diederick E
Jönsson Bo AG
Jeppsson Marina C
Lindh Christian H
Gast Marie-Christine W
Kåredal Monica H
Krop Esmeralda JM
Opstal-van Winden Annemieke WJ
Beijnen Jos H
van Gils Carla H
Vermeulen Roel CH
author_facet Peeters Petra HM
Grobbee Diederick E
Jönsson Bo AG
Jeppsson Marina C
Lindh Christian H
Gast Marie-Christine W
Kåredal Monica H
Krop Esmeralda JM
Opstal-van Winden Annemieke WJ
Beijnen Jos H
van Gils Carla H
Vermeulen Roel CH
author_sort Peeters Petra HM
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected <it>at </it>or <it>after </it>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a<sub>desArg</sub>), 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). C3a<sub>desArg </sub>and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.</p> <p>Conclusions</p> <p>We show that serum protein profiles are already altered up to three years before breast cancer detection.</p>
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spelling doaj.art-cb2517f4f41d4a94a82f4a25a0d9a7272022-12-21T21:07:09ZengBMCBMC Cancer1471-24072011-08-0111138110.1186/1471-2407-11-381Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control studyPeeters Petra HMGrobbee Diederick EJönsson Bo AGJeppsson Marina CLindh Christian HGast Marie-Christine WKåredal Monica HKrop Esmeralda JMOpstal-van Winden Annemieke WJBeijnen Jos Hvan Gils Carla HVermeulen Roel CH<p>Abstract</p> <p>Background</p> <p>Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected <it>at </it>or <it>after </it>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a<sub>desArg</sub>), 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). C3a<sub>desArg </sub>and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.</p> <p>Conclusions</p> <p>We show that serum protein profiles are already altered up to three years before breast cancer detection.</p>http://www.biomedcentral.com/1471-2407/11/381BiomarkersBreast cancerEarly diagnosis2D-nanoLC-MS/MSProspectiveProteomicsSELDI-TOF MS
spellingShingle Peeters Petra HM
Grobbee Diederick E
Jönsson Bo AG
Jeppsson Marina C
Lindh Christian H
Gast Marie-Christine W
Kåredal Monica H
Krop Esmeralda JM
Opstal-van Winden Annemieke WJ
Beijnen Jos H
van Gils Carla H
Vermeulen Roel CH
Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
BMC Cancer
Biomarkers
Breast cancer
Early diagnosis
2D-nanoLC-MS/MS
Prospective
Proteomics
SELDI-TOF MS
title Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
title_full Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
title_fullStr Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
title_full_unstemmed Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
title_short Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
title_sort searching for early breast cancer biomarkers by serum protein profiling of pre diagnostic serum a nested case control study
topic Biomarkers
Breast cancer
Early diagnosis
2D-nanoLC-MS/MS
Prospective
Proteomics
SELDI-TOF MS
url http://www.biomedcentral.com/1471-2407/11/381
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