Identification of N-Glycan Serum Markers Associated with Hepatocellular Carcinoma from Mass Spectrometry Data

Zhiqun Tang, Rency S. Varghese, Slavka Bekesova, Christopher A. Loffredo, Mohamed Abdul Hamid, Zuzana Kyselova§, Yehia Mechref§, Milos V. Novotny§, Radoslav Goldman and Habtom W. Ressom*
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20057, Minia University and Viral Hepatitis Research Laboratory, NHTMRI, Cairo, Egypt, and National Center for Glycomics and Glycoproteomics, Department of Chemistry, Bloomington, Indiana
J. Proteome Res., 2010, 9 (1), pp 104–112
DOI: 10.1021/pr900397n
Publication Date (Web): September 18, 2009
Copyright © 2009 American Chemical Society
* To whom correspondence should be addressed. Habtom W. Ressom, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Suite 173, Building D, 4000 Reservoir Road NW, Washington, D.C. 20057. Phone: 202-687-2283. Fax: 202-687-0227. E-mail: hwr@georgetown.edu., †

Georgetown University.

, ‡

Minia University and Viral Hepatitis Research Laboratory.

, §

National Center for Glycomics and Glycoproteomics.

This article is part of the The Liver Proteome special issue.

Abstract

Abstract Image

Glycocylation represents the most complex and widespread post-translational modifications in human proteins. The variation of glycosylation is closely related to oncogenic transformation. Therefore, profiling of glycans detached from proteins is a promising strategy to identify biomarkers for cancer detection. This study identified candidate glycan biomarkers associated with hepatocellular carcinoma by mass spectrometry. Specifically, mass spectrometry data were analyzed with a peak selection procedure which incorporates multiple random sampling strategies with recursive feature selection based on support vector machines. Ten peak sets were obtained from different combinations of samples. Seven peaks were shared by each of the 10 peaksets, in which 7−12 peaks were selected, indicating 58−100% of peaks were shared by the 10 peaksets. Support vector machines and hierarchical clustering method were used to evaluate the performance of the peaksets. The predictive performance of the seven peaks was further evaluated by using 19 newly generated MALDI-TOF spectra. Glycan structures for four glycans of the seven peaks were determined. Literature search indicated that the structures of the four glycans could be found in some cancer-related glycoproteins. The method of this study is significant in deriving consistent, accurate, and biological significant glycan marker candidates for hepatocellular carcinoma diagnosis.

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History

  • Published In Issue January 04, 2010
  • Article ASAPOctober 05, 2009
  • Just Accepted ManuscriptSeptember 18, 2009
  • Received: May 5, 2009

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