Differential membrane proteomics using 18O-labeling to identify biomarkers for cholangiocarcinoma

Troels Zakarias Kristiansen, H. C. Harsha, Mads Grønborg, Anirban Maitra, Akhilesh Pandey

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Quantitative proteomic methodologies allow profiling of hundreds to thousands of proteins in a high-throughput fashion. This approach is increasingly applied to cancer biomarker discovery to identify proteins that are differentially regulated in cancers. Fractionation of protein samples based on enrichment of cellular subproteomes prior to mass spectrometric analysis can provide increased coverage of certain classes of molecules. We used a membrane protein enrichment strategy coupled with 180 labeling based quantitative proteomics to identify proteins that are highly expressed in cholangiocarcinomas. In addition to identifying several proteins previously known to be overexpressed in cholangiocarcinoma, we discovered a number of molecules that were previously not associated with cholangiocarcinoma. Using immunoblotting and immunohistochemical labeling of tissue microarrays, we validated Golgi membrane protein 1, Annexin IV and Epidermal growth factor receptor pathway substrate 8 (EPS8) as candidate biomarkers for cholangiocarcinomas. Golgi membrane protein 1 was observed to be overexpressed in 89% of cholangiocarcinoma cases analyzed by staining tissue microarrays. In light of recent reports showing that Golgi membrane protein 1 is detectable in serum, further investigation into validation of this protein has the potential to provide a biomarker for early detection of cholangiocarcinomas.

Original languageEnglish (US)
Pages (from-to)4670-4677
Number of pages8
JournalJournal of Proteome Research
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2008

Keywords

  • Gall bladder
  • Immunohistochemistry
  • Liquid chromatography tandem mass spectrometry (LC-MS/MS)
  • O stable isotope labeling
  • Quantitative proteomics
  • Tissue microarrays

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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