N-Glycosylation Patterns Correlate with Hepatocellular Carcinoma Genetic Subtypes

Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths globally, and the incidence rate in the United States is increasing. Studies have identified inter- and intratumor heterogeneity as histologic and/or molecular subtypes/variants associated with response to certain molecular targeted therapies. Spatial HCC tissue profiling of N-linked glycosylation by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) may serve as a new method to evaluate the tumor heterogeneity. Previous work has identified significant changes in the N-linked glycosylation of HCC tumors but has not accounted for the heterogeneous genetic and molecular nature of HCC. To determine the correlation between HCC-specific N-glycosylation changes and genetic/molecular tumor features, we profiled HCC tissue samples with MALDI-IMS and correlated the spatial N-glycosylation with a widely used HCC molecular classification (Hoshida subtypes). MALDI-IMS data displayed trends that could approximately distinguish between subtypes, with subtype 1 demonstrating significantly dysregulated N-glycosylation versus adjacent nontumor tissue. Although there were no individual N-glycan structures that could identify specific subtypes, trends emerged regarding the correlation of branched glycan expression to HCC as a whole and fucosylated glycan expression to subtype 1 tumors specifically.

Automated summary

Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths globally, and studies have identified different histologic and molecular subtypes within tumors that are associated with response to molecular targeted therapies. Spatial profiling of N-linked glycosylation in HCC tissues using MALDI-IMS may provide a new method to evaluate tumor heterogeneity and potential treatment strategies.BTTagCompounded significant changes in N-linked glycosylation in HCC tumors but did not consider the genetic and molecular heterogeneity of HCC, showing trends in glycan expressions that correlated with HCC molecular subtypes.