Department of Chemistry, University of California, Davis, California, USA.
Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
J Cell Physiol. 2024 Mar;239(3):e31147. doi: 10.1002/jcp.31147. Epub 2023 Nov 3.
Secreted proteins are overexpressed in cholangiocarcinoma (CCA) and actively involved in promoting metastatic spread. Many of these proteins possess one or more sites of glycosylation and their various glycoforms have potential utility as prognostic or diagnostic biomarkers. To evaluate the effects of secretome glycosylation on patient outcome, we elucidated the glycosylation patterns of proteins secreted by parental and metastatic CCA cells using liquid chromatography-mass spectrometry. Our analysis showed that the secretome of CCA cells was dominated by fucosylated and fucosialylated glycoforms. Based on the glycan and protein profiles, we evaluated the combined prognostic significance of glycosyltransferases and secretory proteins. Significantly, genes encoding fucosyltransferases and sialyltransferases showed favorable prognostic effects when combined with secretory protein-coding gene expression, particularly thrombospondin-1. Combining these measures may provide improved risk assessment for CCA and be used to indicate stages of disease progression.
分泌蛋白在胆管癌（CCA）中过度表达，并积极参与促进转移扩散。这些蛋白中的许多都具有一个或多个糖基化位点，其各种糖型可能作为预后或诊断生物标志物具有潜在的用途。为了评估分泌组糖基化对患者预后的影响，我们使用液相色谱-质谱法阐明了亲本和转移性 CCA 细胞分泌的蛋白质的糖基化模式。我们的分析表明，CCA 细胞的分泌组主要由岩藻糖基化和岩藻糖化糖型组成。基于聚糖和蛋白质谱，我们评估了糖基转移酶和分泌蛋白的联合预后意义。重要的是，当与分泌蛋白编码基因表达结合时，编码岩藻糖基转移酶和唾液酸转移酶的基因显示出有利的预后效果，尤其是血栓素-1。结合这些措施可能为 CCA 提供更好的风险评估，并用于指示疾病进展阶段。
