Identification of N-glycan serum markers associated with hepatocellular carcinoma from mass spectrometry data.
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.
Tang
Zhiqun
Z
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Varghese
Rency S
RS
Bekesova
Slavka
S
Loffredo
Christopher A
CA
Hamid
Mohamed Abdul
MA
Kyselova
Zuzana
Z
Mechref
Yehia
Y
Novotny
Milos V
MV
Goldman
Radoslav
R
Ressom
Habtom W
HW
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016000:Cluster Analysis; D006031:Glycosylation; D006801:Humans; D011134:Polysaccharides / Q000097:blood* / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D014408:Biomarkers, Tumor; D011134:Polysaccharides