Sistema de Salut de Catalunya
Institut Català de la Salut
[Kohansal-Nodehi M, Swiatek-de Lange M, Kroeniger K, Rolny V, Tabarés G] Roche Diagnostics GmbH, Research and Development Core Lab, Penzberg, Germany. [Piratvisuth T] NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand. [Esteban JI] Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-11-16T13:44:17Z
2023-11-16T13:44:17Z
2023-10-18
Glycoproteomics; Haptoglobin; Hepatocellular carcinoma
Glicoproteómica; Haptoglobina; Carcinoma hepatocelular
Glicoproteòmica; Haptoglobina; Carcinoma hepatocel·lular
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.
This analysis was funded by Roche Diagnostics GmbH.
Article
Published version
English
Fenotip; Glicopèptids; Marcadors bioquímics; Càncer - Detecció precoç; Fetge - Càncer - Diagnòstic; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Early Diagnosis::Early Detection of Cancer; CHEMICALS AND DRUGS::Biological Factors::Biomarkers; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Acute-Phase Proteins::Haptoglobins; PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::diagnóstico precoz::detección precoz del cáncer; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::proteínas de fase aguda::haptoglobinas; FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::carcinoma hepatocelular
Frontiers Media
Frontiers in Oncology;13
https://doi.org/10.3389/fonc.2023.1213898
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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