Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma
Issued Date
2023-01-01
Resource Type
eISSN
2234943X
Scopus ID
2-s2.0-85175608581
Journal Title
Frontiers in Oncology
Volume
13
Rights Holder(s)
SCOPUS
Bibliographic Citation
Frontiers in Oncology Vol.13 (2023)
Suggested Citation
Kohansal-Nodehi M., Swiatek-de Lange M., Kroeniger K., Rolny V., Tabarés G., Piratvisuth T., Tanwandee T., Thongsawat S., Sukeepaisarnjaroen W., Esteban J.I., Bes M., Köhler B., Chan H.L.Y., Busskamp H. Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma. Frontiers in Oncology Vol.13 (2023). doi:10.3389/fonc.2023.1213898 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91010
Title
Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma
Author's Affiliation
Siriraj Hospital
Chinese University of Hong Kong, Faculty of Medicine
Roche Diagnostics GmbH
Faculty of Medicine, Khon Kaen University
Centro de Transfusion y Banco de Tejidos
Hospital Universitari Vall d'Hebron
Prince of Songkla University
Universitätsklinikum Heidelberg
Chiang Mai University
Liver Cancer Center Heidelberg (LCCH)
Chinese University of Hong Kong, Faculty of Medicine
Roche Diagnostics GmbH
Faculty of Medicine, Khon Kaen University
Centro de Transfusion y Banco de Tejidos
Hospital Universitari Vall d'Hebron
Prince of Songkla University
Universitätsklinikum Heidelberg
Chiang Mai University
Liver Cancer Center Heidelberg (LCCH)
Other Contributor(s)
Abstract
Background: There is a need for new serum biomarkers for early detection of hepatocellular carcinoma (HCC). Haptoglobin (Hp) N-glycosylation is altered in HCC, but the diagnostic value of site-specific Hp glycobiomarkers is rarely reported. We aimed to determine the site-specific glycosylation profile of Hp for early-stage HCC diagnosis. Method: Hp glycosylation was analyzed in the plasma of patients with liver diseases (n=57; controls), early-stage HCC (n=50) and late-stage HCC (n=32). Hp phenotype was determined by immunoblotting. Hp was immunoisolated and digested into peptides. N-glycopeptides were identified and quantified using liquid chromatography–mass spectrometry. Cohort samples were compared using Wilcoxon rank-sum (Mann-Whitney U) tests. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and area under curve (AUC). Results: Significantly higher fucosylation, branching and sialylation of Hp glycans, and expression of high-mannose glycans, was observed as disease progressed from cirrhosis to early- and late-stage HCC. Several glycopeptides demonstrated high values for early diagnosis of HCC, with an AUC of 93% (n=1), >80% (n=3), >75% (n=13) and >70% (n=11), compared with alpha-fetoprotein (AFP; AUC of 79%). The diagnostic performance of the identified biomarkers was only slightly affected by Hp phenotype. Conclusion: We identified a panel of Hp glycopeptides that are significantly differentially regulated in early- and late-stage HCC. Some glycobiomarkers exceeded the diagnostic value of AFP (the most commonly used biomarker for HCC diagnosis). Our findings provide evidence that glycobiomarkers can be effective in the diagnosis of early HCC – individually, as a panel of glycopeptides or combined with conventional serological biomarkers.