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

BMC Cancer, 08/29/2011

Opstal-van Winden AWJ et al. – The authors show that serum protein profiles are already altered up to three years before breast cancer detection.

Methods

  • Nested case-control design we compared 68 women diagnosed with breast cancer within 3 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)
  • Subset of 20 case-control pairs
  • Serum proteome 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

  • 2 SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), higher in pre-diagnostic breast cancer serum (p=0.02 and p=0.06)
  • With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) 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 presence of symptomatic and/or mammographically detectable breast cancer

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