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. Implications: Correlating N-glycosylation to specific subtypes offers the specific detection of subtypes of HCC, which could both enhance early HCC sensitivity and guide targeted clinical therapies.

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N-糖基化模式与肝细胞癌遗传亚型相关

肝细胞癌（HCC）是全球第二大癌症死亡原因，并且在美国的发病率正在上升。研究已将肿瘤间和肿瘤内异质性确定为与某些分子靶向治疗的反应相关的组织学和/或分子亚型/变异。通过基质辅助激光解吸电离成像质谱（MALDI-IMS）对 N-连接糖基化进行空间 HCC 组织分析可能作为评估肿瘤异质性的新方法。先前的工作已经确定了 HCC 肿瘤 N 连接糖基化的显着变化，但尚未解释 HCC 的异质遗传和分子性质。为了确定 HCC 特异性 N-糖基化变化与遗传/分子肿瘤特征之间的相关性，我们使用 MALDI-IMS 对 HCC 组织样本进行了分析，并将空间 N-糖基化与广泛使用的 HCC 分子分类（Hoshida 亚型）相关联。MALDI-IMS 数据显示的趋势可以大致区分亚型，其中亚型 1 表现出与邻近非肿瘤组织相比显着失调的 N-糖基化。尽管没有单独的 N-聚糖结构可以识别特定亚型，但支链聚糖表达与整个 HCC 的相关性以及岩藻糖基化聚糖表达与 1 亚型肿瘤的相关性出现了趋势。意义：将 N-糖基化与特定亚型相关联可以对 HCC 亚型进行特异性检测，这既可以增强早期 HCC 的敏感性，也可以指导靶向临床治疗。