Combined analysis of secreted proteins and glycosylation identifies prognostic features in cholangiocarcinoma

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...

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Bibliographic Details
Published in:Journal of cellular physiology 2024-03, Vol.239 (3), p.e31147-n/a
Main Authors: Park, Diane Dayoung, Xu, Gege, Park, Simon S., Haigh, Nathan E., Phoomak, Chatchai, Wongkham, Sopit, Maverakis, Emanual, Lebrilla, Carlito B.
Format: Article
Language:English
Subjects:
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Biomarkers
Cell Line, Tumor
Cholangiocarcinoma
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
Disease Progression
Evaluation
Gene expression
Glycan
Glycoproteins - metabolism
Glycosylation
Humans
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Metastases
metastasis
Polysaccharides - metabolism
Prognosis
Proteins
Risk assessment
secreted proteins
Secretome
survival
Thrombospondin
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Summary: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. Changes in fucosylation and sialylation were associated with the secretome of metastatic cholangiocarcinoma (CCA). A survival analysis across secreted protein‐coding genes revealed a more favorable prognostic effect when combined with fucosyltransferase‐ or sialyltransferase‐coding genes than when evaluated individually. Glycosylation enzymes improved the prognostic value of secreted proteins in CCA.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.31147