LC–MS Profiling of N‑Glycans Derived from Human Serum Samples for Biomarker Discovery in Hepatocellular Carcinoma

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.