Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma

• Verfasst von: Kohansal-Nodehi, Mahdokht [VerfasserIn]
• Verfasst von: Swiatek-de Lange, Magdalena [VerfasserIn]
• Verfasst von: Kroeniger, Konstantin [VerfasserIn]
• Verfasst von: Rolny, Vinzent [VerfasserIn]
• Verfasst von: Tabarés, Glòria [VerfasserIn]
• Verfasst von: Piratvisuth, Teerha [VerfasserIn]
• Verfasst von: Tanwandee, Tawesak [VerfasserIn]
• Verfasst von: Thongsawat, Satawat [VerfasserIn]
• Verfasst von: Sukeepaisarnjaroen, Wattana [VerfasserIn]
• Verfasst von: Esteban, Juan Ignacio [VerfasserIn]
• Verfasst von: Bes, Marta [VerfasserIn]
• Verfasst von: Köhler, Bruno Christian [VerfasserIn]
• Verfasst von: Chan, Henry Lik-Yuen [VerfasserIn]
• Verfasst von: Busskamp, Holger [VerfasserIn]
• Titel: Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma
• Verf.angabe: Mahdokht Kohansal-Nodehi, Magdalena Swiatek-de Lange, Konstantin Kroeniger, Vinzent Rolny, Glòria Tabarés, Teerha Piratvisuth, Tawesak Tanwandee, Satawat Thongsawat, Wattana Sukeepaisarnjaroen, Juan Ignacio Esteban, Marta Bes, Bruno Köhler, Henry Lik-Yuen Chan and Holger Busskamp
• E-Jahr: 2023
• Jahr: 18 October 2023
• Umfang: 14 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 06.12.2023
• Titel Quelle: Enthalten in: Frontiers in oncology
• Ort Quelle: Lausanne : Frontiers Media, 2011
• Jahr Quelle: 2023
• Band/Heft Quelle: 13(2023) vom: Okt., Artikel-ID 1213898, Seite 1-14
• ISSN Quelle: 2234-943X
• DOI: doi:10.3389/fonc.2023.1213898
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1872132944

Abstract

BackgroundThere 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.MethodHp 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).ResultsSignificantly 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.ConclusionWe 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.