LC鈥揗S Profiling of N-Glycans Derived from Human Serum Samples for Biomarker Discovery in Hepatocellular Carcinoma
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- 作者：Tsung-Heng Tsai ; Minkun Wang ; Cristina Di Poto ; Yunli Hu ; Shiyue Zhou ; Yi Zhao ; Rency S. Varghese ; Yue Luo ; Mahlet G. Tadesse ; Dina Hazem Ziada ; Chirag S. Desai ; Kirti Shetty ; Yehia Mechref ; Habtom W. Ressom
- 刊名：Journal of Proteome Research
- 出版年：2014
- 出版时间：November 7, 2014
- 年：2014
- 卷：13
- 期：11
- 页码：4859-4868
- 全文大小：573K
- ISSN：1535-3907
文摘
Defining clinically relevant biomarkers for early stage hepatocellular carcinoma (HCC) in a high-risk population of cirrhotic patients has potentially far-reaching implications for disease management and patient health. Changes in glycan levels have been associated with the onset of numerous diseases including cancer. In the present study, we used liquid chromatography coupled with electrospray ionization mass spectrometry (LC鈥揈SI-MS) to analyze N-glycans in sera from 183 participants recruited in Egypt and the U.S. and identified candidate biomarkers that distinguish HCC cases from cirrhotic controls. N-Glycans were released from serum proteins and permethylated prior to the LC鈥揈SI-MS analysis. Through two complementary LC鈥揈SI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls. These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis. The results of this study illustrate the power of the integrative approach combining complementary LC鈥揈SI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.