Novel breast cancer biomarkers identified by integrative proteomic and gene expression mapping

J Proteome Res. 2008 Apr;7(4):1518-28. doi: 10.1021/pr700820g. Epub 2008 Mar 5.


Proteomic and transcriptomic platforms both play important roles in cancer research, with differing strengths and limitations. Here, we describe a proteo-transcriptomic integrative strategy for discovering novel cancer biomarkers, combining the direct visualization of differentially expressed proteins with the high-throughput scale of gene expression profiling. Using breast cancer as a case example, we generated comprehensive two-dimensional electrophoresis (2DE)/mass spectrometry (MS) proteomic maps of cancer (MCF-7 and HCC-38) and control (CCD-1059Sk) cell lines, identifying 1724 expressed protein spots representing 484 different protein species. The differentially expressed cell-line proteins were then mapped to mRNA transcript databases of cancer cell lines and primary breast tumors to identify candidate biomarkers that were concordantly expressed at the gene expression level. Of the top nine selected biomarker candidates, we reidentified ANX1, a protein previously reported to be differentially expressed in breast cancers and normal tissues, and validated three other novel candidates, CRAB, 6PGL, and CAZ2, as differentially expressed proteins by immunohistochemistry on breast tissue microarrays. In total, close to half (4/9) of our protein biomarker candidates were successfully validated. Our study thus illustrates how the systematic integration of proteomic and transcriptomic data from both cell line and primary tissue samples can prove advantageous for accelerating cancer biomarker discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A1 / analysis
  • Annexin A1 / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • CapZ Actin Capping Protein / analysis
  • CapZ Actin Capping Protein / genetics
  • Carboxylic Ester Hydrolases / analysis
  • Carboxylic Ester Hydrolases / genetics
  • Cell Line, Tumor
  • Computational Biology
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Proteome / analysis*
  • Proteome / genetics
  • Proteomics / methods*
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tissue Array Analysis / methods
  • alpha-Crystallin B Chain / analysis
  • alpha-Crystallin B Chain / genetics


  • Annexin A1
  • Biomarkers, Tumor
  • CAPZA2 protein, human
  • CRYAB protein, human
  • CapZ Actin Capping Protein
  • Proteome
  • alpha-Crystallin B Chain
  • Carboxylic Ester Hydrolases
  • 6-phosphogluconolactonase