LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma

Tsung Heng Tsai, Ehwang Song, Rui Zhu, Cristina Di Poto, Minkun Wang, Yue Luo, Rency S. Varghese, Mahlet G. Tadesse, Dina Hazem Ziada, Chirag S. Desai, Kirti Shetty, Yehia Mechref, Habtom W. Ressom

Research output: Contribution to journalArticle

Abstract

Associating changes in protein levels with the onset of cancer has been widely investigated to identify clinically relevant diagnostic biomarkers. In the present study, we analyzed sera from 205 patients recruited in the United States and Egypt for biomarker discovery using label-free proteomic analysis by LC-MS/MS. We performed untargeted proteomic analysis of sera to identify candidate proteins with statistically significant differences between hepatocellular carcinoma (HCC) and patients with liver cirrhosis. We further evaluated the significance of 101 proteins in sera from the same 205 patients through targeted quantitation by MRM on a triple quadrupole mass spectrometer. This led to the identification of 21 candidate protein biomarkers that were significantly altered in both the United States and Egyptian cohorts. Among the 21 candidates, ten were previously reported as HCC-associated proteins (eight exhibiting consistent trends with our observation), whereas 11 are new candidates discovered by this study. Pathway analysis based on the significant proteins reveals upregulation of the complement and coagulation cascades pathway and downregulation of the antigen processing and presentation pathway in HCC cases versus patients with liver cirrhosis. The results of this study demonstrate the power of combining untargeted and targeted quantitation methods for a comprehensive serum proteomic analysis, to evaluate changes in protein levels and discover novel diagnostic biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD001171 (http://proteomecentral.proteomexchange.org/dataset/PXD001171).

Original languageEnglish (US)
Pages (from-to)2369-2381
Number of pages13
JournalProteomics
Volume15
Issue number13
DOIs
StatePublished - Jul 1 2015

Fingerprint

Biomarkers
Proteomics
Hepatocellular Carcinoma
Serum
Proteins
Antigen Presentation
Liver Cirrhosis
Liver
Egypt
Mass spectrometers
Coagulation
Blood Proteins
Up-Regulation
Down-Regulation
Labels
Observation
Antigens
Processing
Neoplasms

Keywords

  • Biomedicine
  • Cancer biomarker discovery
  • Hepatocellular carcinoma
  • LC-MS/MS
  • Liver cirrhosis
  • MRM

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Tsai, T. H., Song, E., Zhu, R., Di Poto, C., Wang, M., Luo, Y., ... Ressom, H. W. (2015). LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma. Proteomics, 15(13), 2369-2381. https://doi.org/10.1002/pmic.201400364

LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma. / Tsai, Tsung Heng; Song, Ehwang; Zhu, Rui; Di Poto, Cristina; Wang, Minkun; Luo, Yue; Varghese, Rency S.; Tadesse, Mahlet G.; Ziada, Dina Hazem; Desai, Chirag S.; Shetty, Kirti; Mechref, Yehia; Ressom, Habtom W.

In: Proteomics, Vol. 15, No. 13, 01.07.2015, p. 2369-2381.

Research output: Contribution to journalArticle

Tsai, TH, Song, E, Zhu, R, Di Poto, C, Wang, M, Luo, Y, Varghese, RS, Tadesse, MG, Ziada, DH, Desai, CS, Shetty, K, Mechref, Y & Ressom, HW 2015, 'LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma', Proteomics, vol. 15, no. 13, pp. 2369-2381. https://doi.org/10.1002/pmic.201400364
Tsai, Tsung Heng ; Song, Ehwang ; Zhu, Rui ; Di Poto, Cristina ; Wang, Minkun ; Luo, Yue ; Varghese, Rency S. ; Tadesse, Mahlet G. ; Ziada, Dina Hazem ; Desai, Chirag S. ; Shetty, Kirti ; Mechref, Yehia ; Ressom, Habtom W. / LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma. In: Proteomics. 2015 ; Vol. 15, No. 13. pp. 2369-2381.
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