Dissecting characteristics and dynamics of differentially expressed proteins during multistage carcinogenesis of human colorectal cancer

World J Gastroenterol. 2016 May 14;22(18):4515-28. doi: 10.3748/wjg.v22.i18.4515.

Abstract

Aim: To discover novel biomarkers for early diagnosis, prognosis or treatment of human colorectal cancer.

Methods: iTRAQ 2D LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in the human colonic epithelial carcinogenic process using laser capture microdissection-purified colonic epithelial cells from normal colon, adenoma, carcinoma in situ and invasive carcinoma tissues.

Results: A total of 326 DEPs were identified, and four DEPs (DMBT1, S100A9, Galectin-10, and S100A8) with progressive alteration in the carcinogenic process were further validated by immunohistochemistry. The DEPs were involved in multiple biological processes including cell cycle, cell adhesion, translation, mRNA processing, and protein synthesis. Some of the DEPs involved in cellular process such as "translation" and "mRNA splicing" were progressively up-regulated, while some DEPs involved in other processes such as "metabolism" and "cell response to stress" was progressively down-regulated. Other proteins with up- or down-regulation at certain stages of carcinogenesis may play various roles at different stages of the colorectal carcinogenic process.

Conclusion: These findings give insights into our understanding of the mechanisms of colorectal carcinogenesis and provide clues for further investigation of carcinogenesis and identification of biomarkers.

Keywords: Biomarker; Carcinogenesis; Colorectal Cancer; Proteome.

Publication types

  • Comparative Study

MeSH terms

  • Adenoma / chemistry*
  • Adenoma / pathology
  • Biomarkers, Tumor / analysis*
  • Calcium-Binding Proteins
  • Calgranulin A / analysis
  • Calgranulin B / analysis
  • Carcinoma / chemistry*
  • Carcinoma / pathology
  • Carcinoma in Situ / chemistry*
  • Carcinoma in Situ / pathology
  • Cell Transformation, Neoplastic / chemistry*
  • Cell Transformation, Neoplastic / pathology
  • Chromatography, Liquid
  • Colorectal Neoplasms / chemistry*
  • Colorectal Neoplasms / pathology
  • Computational Biology
  • DNA-Binding Proteins
  • Early Detection of Cancer / methods
  • Galectins / analysis
  • Humans
  • Immunohistochemistry
  • Laser Capture Microdissection
  • Predictive Value of Tests
  • Proteomics / methods
  • Receptors, Cell Surface / analysis
  • Tandem Mass Spectrometry
  • Tumor Suppressor Proteins

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Calgranulin A
  • Calgranulin B
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Galectins
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • galectin 10, human