Loss of clusterin both in serum and tissue correlates with the tumorigenesis of esophageal squamous cell carcinoma via proteomics approaches

World J Gastroenterol. 2003 Apr;9(4):650-4. doi: 10.3748/wjg.v9.i4.650.


Aim: To identify the differentially secreted proteins or polypeptides associated with tumorigenesis of esophageal squamous cell carcinoma (ESCC) from serum and to find potential tumor secreted biomarkers.

Methods: Proteins from human ESCC tissue and its matched adjacent normal tissue; pre-surgery and post-surgery serum; and pre-surgery and normal control serum were separated by two-dimensional electrophoresis (2-DE) to identify differentially expressed proteins. The silver-stained 2-DE were scanned with digital ImageScanner and analyzed with ImageMaster 2D Elite 3.10 software. A cluster of protein spots differentially expressed were selected and identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). One of the differentially expressed proteins, clusterin, was down-regulated in cancer tissue and pre-surgery serum, but it was reversed in post-surgery serum. The results were confirmed by semi-quantitative reverse-transcription (RT)-PCR and western blot.

Results: Comparisons of the protein spots identified on the 2-DE maps from human matched sera showed that some proteins were differentially expressed, with most of them showing no differences in composition, shape or density. Being analyzed by MALDI-TOF-MS and database searching, clusterin was differentially expressed and down-regulated in both cancer tissue and pre-surgery serum compared with their counterparts. The results were also validated by RT-PCR and western blot.

Conclusion: The differentially expressed clusterin may play a key role during tumorigenesis of ESCC. The 2DE-MS based proteomic approach is one of the powerful tools for discovery of secreted markers from peripheral.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Biomarkers, Tumor / blood
  • Blotting, Western
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery
  • Clusterin
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Female
  • Glycoproteins / blood
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Molecular Chaperones / blood
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Peptide Fragments / chemistry
  • Proteome*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Biomarkers, Tumor
  • CLU protein, human
  • Clusterin
  • Glycoproteins
  • Molecular Chaperones
  • Neoplasm Proteins
  • Peptide Fragments
  • Proteome