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

Frontiers in Oncology

Oncology

Satawat Thongsawat¹  Bruno Köhler²  Tawesak Tanwandee³  Wattana Sukeepaisarnjaroen⁴  Henry Lik-Yuen Chan⁵  Juan Ignacio Esteban⁶  Teerha Piratvisuth⁷  Vinzent Rolny⁸  Mahdokht Kohansal-Nodehi⁸  Konstantin Kroeniger⁸  Glòria Tabarés⁸  Holger Busskamp⁸  Magdalena Swiatek-de Lange⁸  Marta Bes⁹ 

[1] Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University, Chiang Mai, Thailand;Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany;Liver Cancer Center Heidelberg, Heidelberg, Germany;Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand;Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;Liver Unit, Hospital Universitari Vall d’Hebron (HUVH), Barcelona, Spain;NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand;Roche Diagnostics GmbH, Research and Development Core Lab, Penzberg, Germany;Transfusion Safety Laboratory, Banc de Sang i Teixits (BST), Barcelona, Spain;

关键词: haptoglobin;    glycosylation;    biomarker;    glycoproteomics;    hepatocellular carcinoma;    diagnostics;   

DOI  :  10.3389/fonc.2023.1213898

 received in 2023-04-28, accepted in 2023-09-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Kohansal-Nodehi, Swiatek-de Lange, Kroeniger, Rolny, Tabarés, Piratvisuth, Tanwandee, Thongsawat, Sukeepaisarnjaroen, Esteban, Bes, Köhler, Chan and Busskamp