title: LC-MS profiling of N-Glycans derived from human serum samples for biomarker discovery in hepatocellular carcinoma.
abstract: 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-ESI-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-ESI-MS analysis. Through two complementary LC-ESI-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-ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.
authors: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington, DC 20057, United States.
authors: Tsung-Heng
authors: TH
authors: Tsai
authors: Minkun
authors: M
authors: Wang
authors: Cristina
authors: C
authors: Di Poto
authors: Yunli
authors: Y
authors: Hu
authors: Shiyue
authors: S
authors: Zhou
authors: Yi
authors: Y
authors: Zhao
authors: Rency S
authors: RS
authors: Varghese
authors: Yue
authors: Y
authors: Luo
authors: Mahlet G
authors: MG
authors: Tadesse
authors: Dina Hazem
authors: DH
authors: Ziada
authors: Chirag S
authors: CS
authors: Desai
authors: Kirti
authors: K
authors: Shetty
authors: Yehia
authors: Y
authors: Mechref
authors: Habtom W
authors: HW
authors: Ressom
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D002853:Chromatography, Liquid; D004534:Egypt; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D013058:Mass Spectrometry; D011134:Polysaccharides / Q000097:blood*; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D011134:Polysaccharides
keywords: cancer biomarker discovery; glycomics; hepatocellular carcinoma; liver cirrhosis; mass spectrometry; multiple reaction monitoring