Individualised proteome profiling of human endometrial tumours improves detection of new prognostic markers

Br J Cancer. 2013 Aug 6;109(3):704-13. doi: 10.1038/bjc.2013.359. Epub 2013 Jul 9.

Abstract

Background: The individual features of tumours are often disregarded in cohort studies. As these features may represent a source for individualised cancer treatment, it is important to develop a novel approach for their assessment.

Methods: We used proteomics, systems biology, and immunohistochemistry to explore protein expression in human endometrial tumours, to identify deregulated regulatory mechanisms, and to validate observed changes in protein expression using tissue microarrays.

Results: Compared with the evaluation of common tumour features, the evaluation of individual tumour features gave a more comprehensive and detailed overview of the regulatory processes in endometrial tumours. Systemic analysis of the individual proteome profiles showed that endometrial tumours employed different proteins to regulate similar functions. Comparison of our data with publicly available data sets of molecular profiling of human endometrial tumours confirmed that individual tumour features are not simply irrelevant individual variations, but are indeed important in endometrial tumorigenesis. Validation through tissue microarray investigation of MST1 and PKN1 proteins confirmed the usefulness of this approach, and suggested that MST1 and PKN1 may be considered as predictive biomarkers of endometrial cancer.

Conclusion: We show that individualised profiling of endometrial tumours may deliver better insights into a tumour's physiology, thereby giving a better prediction of tumour development. Individual tumour features may also be used to tailor cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Down-Regulation
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Precision Medicine / methods*
  • Prognosis
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proteome / genetics
  • Proteome / metabolism*
  • Proteomics / methods
  • Systems Biology / methods

Substances

  • Intracellular Signaling Peptides and Proteins
  • Proteome
  • protein kinase N
  • STK4 protein, human
  • Protein Serine-Threonine Kinases
  • Protein Kinase C