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

Opstal-van Winden, Annemieke W. J.; Krop, Esmeralda J. M.; Kåredal, Monica LU ; Gast, Marie-Christine W.; Lindh, Christian LU ; Jeppsson, Marina LU ; Jönsson, Bo A LU ; Grobbee, Diederick E.; Peeters, Petra H. M. and Beijnen, Jos H., et al. (2011) In BMC Cancer 11.
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... (More)
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 (C3a(desArg)), 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(desArg) 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. (Less)
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keywords
Biomarkers, Breast cancer, Early diagnosis, 2D-nanoLC-MS/MS, Prospective, Proteomics, SELDI-TOF MS
in
BMC Cancer
volume
11
publisher
BioMed Central
external identifiers
  • wos:000295720500001
  • scopus:80052038610
ISSN
1471-2407
DOI
10.1186/1471-2407-11-381
language
English
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yes
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b70b74d6-0db8-4b7d-aa00-d728afb8e62b (old id 2212910)
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2011-12-01 08:29:15
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2017-08-20 03:49:59
@article{b70b74d6-0db8-4b7d-aa00-d728afb8e62b,
  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 (C3a(desArg)), 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 &lt; 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p &lt; 0.05). C3a(desArg) 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.},
  author       = {Opstal-van Winden, Annemieke W. J. and Krop, Esmeralda J. M. and Kåredal, Monica and Gast, Marie-Christine W. and Lindh, Christian and Jeppsson, Marina and Jönsson, Bo A and Grobbee, Diederick E. and Peeters, Petra H. M. and Beijnen, Jos H. and van Gils, Carla H. and Vermeulen, Roel C. H.},
  issn         = {1471-2407},
  keyword      = {Biomarkers,Breast cancer,Early diagnosis,2D-nanoLC-MS/MS,Prospective,Proteomics,SELDI-TOF MS},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study},
  url          = {http://dx.doi.org/10.1186/1471-2407-11-381},
  volume       = {11},
  year         = {2011},
}