Combined analysis of secreted proteins and glycosylation identifies prognostic features in cholangiocarcinoma |
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| Authors: | Diane Dayoung Park Gege Xu Simon S. Park Nathan E. Haigh Chatchai Phoomak Sopit Wongkham Emanual Maverakis Carlito B. Lebrilla |
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| Affiliation: | 1. Department of Chemistry, University of California, Davis, California, USA;2. Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA;3. Department of Dermatology, Davis School of Medicine, University of California, Sacramento, California, USA;4. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand |
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| Abstract: | 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. |
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| Keywords: | cholangiocarcinoma glycosylation metastasis secreted proteins survival |
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