A quantitative proteomic approach for identification of potential biomarkers in hepatocellular carcinoma

Raghothama Chaerkady, H. C. Harsha, Anuradha Nalli, Marjan Gucek, Perumal Vivekanandan, Javed Akhtar, Robert N. Cole, Jessica Simmers, Richard D. Schulick, Sujay Singh, Michael Torbenson, Akhilesh Pandey, Paul J. Thuluvath

Research output: Contribution to journalArticle

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. In this study, our objective was to identify differentially regulated proteins in HCC through a quantitative proteomic approach using iTRAQ. More than 600 proteins were quantitated of which 59 proteins were overexpressed and 92 proteins were underexpressed in HCC as compared to adjacent normal tissue. Several differentially expressed proteins were not implicated previously in HCC. A subset of these proteins (six each from upregulated and downregulated groups) was further validated using immunoblotting and immuno-histochemical labeling. Some of the overexpressed proteins with no previous description in the context of HCC include fibroleukin, interferon induced 56 kDa protein, milk fat globule-EGF factor 8, and myeloid-associated differentiation marker. Interestingly, all the enzymes of urea metabolic pathway were dramatically downregulated. Immunohistochemical labeling confirmed differential expression of fibroleukin, myeloid associated differentiation marker and ornithine carbamoyl transferase in majority of HCC samples analyzed. Our results demonstrate quantitative proteomics as a robust discovery tool for the identification of differentially regulated proteins in cancers.

Original languageEnglish (US)
Pages (from-to)4289-4298
Number of pages10
JournalJournal of proteome research
Volume7
Issue number10
DOIs
StatePublished - Oct 1 2008

Keywords

  • Fibroleukin
  • HCV
  • Liver
  • Mass spectrometry
  • Myeloid-associated differentiation marker
  • Strong cation exchange chromatography
  • Urea cycle
  • iTRAQ

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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  • Cite this

    Chaerkady, R., Harsha, H. C., Nalli, A., Gucek, M., Vivekanandan, P., Akhtar, J., Cole, R. N., Simmers, J., Schulick, R. D., Singh, S., Torbenson, M., Pandey, A., & Thuluvath, P. J. (2008). A quantitative proteomic approach for identification of potential biomarkers in hepatocellular carcinoma. Journal of proteome research, 7(10), 4289-4298. https://doi.org/10.1021/pr800197z