Mining the malignant ascites proteome for pancreatic cancer biomarkers

Proteomics. 2011 Dec;11(23):4551-8. doi: 10.1002/pmic.201100264. Epub 2011 Oct 28.

Abstract

Pancreatic cancer (PC) is one of the most lethal malignancies and disease-specific biomarkers are desperately needed for better diagnosis, prognosis, monitoring treatment efficacy and for accelerating the development of novel targeted therapeutics. Being an advanced stage manifestation and a proximal fluid in contact with cancer tissues, the ascitic fluid presents itself as a promising rich source of biomarkers. Herein, we present a comprehensive proteomic analysis of pancreatic ascitic fluid. To fractionate the complex ascites proteome, we adopted a multi-dimensional chromatographic approach that included size-exclusion, ion-exchange and lectin-affinity chromatographic techniques. Our detailed proteomic analysis with high-resolution Orbitrap(®) mass spectrometer resulted in the identification of 816 proteins. We followed rigorous filtering criteria that consisted of PC-specific information obtained from three publicly available databases (Oncomine, Protein Atlas and Unigene) to segregate 20 putative biomarker candidates for future validation. Since these proteins are of membranous and extra-cellular origin, most are glycosylated, and many of them are over-expressed in cancer tissues, the probability of these proteins entering the peripheral blood circulation is high. Their validation as serological PC biomarkers in the future is highly warranted.

MeSH terms

  • Aged
  • Ascites / metabolism*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / isolation & purification
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreas / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Proteome / analysis*
  • Proteome / isolation & purification
  • Proteome / metabolism
  • Proteomics / methods*

Substances

  • Biomarkers, Tumor
  • Proteome