Glycoproteomics-based Liquid-biopsy LDT Development Service for Hepatocellular Carcinoma (HCC)

Importance of Glycosylation in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a predominant form of liver cancer. A noteworthy challenge lies in the fact that over 80% of HCC cases are intertwined with underlying liver cirrhosis, obscuring the initial signs of HCC development. α-fetoprotein (AFP) is a well-established HCC serum biomarker, however, the sensitivity and predictive accuracy continue to fall short in enabling early-stage HCC detection.

Glycosylation patterns associated with cancer offer a basis for the exploration of novel biomarkers. The broader phenomenon of aberrant glycosylation, and specifically the escalated fucosylation catalyzed by fucosyltransferases, has gained prominence as a discerning indicator of the progression from liver disease to HCC. The core fucosylated variant of AFP (AFP-L3), has emerged as a superior biomarker for HCC in comparison to the conventional AFP marker. Furthermore, several other serum glycoproteins, including haptoglobin (Hp), α-1-acid glycoprotein (AGP), α-1-antichymotrypsin (AACT), and hemopexin (HPX), have been documented to manifest augmented fucosylation. This comprehensive characterization and quantitative assessment of serum glycosylation, especially fucosylated forms, is imperative for early-stage HCC detection.

Glycoproteomics-based Liquid-biopsy LDT Development for HCC at Creative Biolabs

Creative Biolabs takes great pride in introducing our pioneering glycoproteomics-based liquid-biopsy LDT development for HCC. Recognizing the pivotal significance of aberrant fucosylation in disease initiation and progression, we have developed an advanced platform for in-depth analysis of intact Fuc glycopeptides for site-specific analysis based on our liquid-biopsy LDT development.

Fig.1 LDT development for Fuc glycopeptides profiling.

Our LDT platform is primarily centered around a lectin-coupled mass spectrometry (MS) strategy aimed at discerning variations in overall fucosylated glycoproteins between HCC samples at different stages and normal samples. The fucosylated peptides are selectively enriched using Lens culinaris agglutinin (LCA). The captured peptides are then subjected to analysis via nano-liquid chromatography coupled with matrix-assisted laser desorption/ionization tandem mass spectrometry (nano-LC-MALDI-MS/MS). Finally, MS data analysis is performed by in-house developed software with robust glycopeptide search capabilities.

Highlights

Published Data

Technology: Glycoproteomic analysis

Journal: Journal of Proteome Research

Published: 2020

Results: The bifucosylated tri- and tetra-antennary glycoforms in serum Hp were significantly increased in NASH-related HCC compared to cirrhosis. Evaluation of the diagnostic performance showed that the N-glycopeptides at sites of N184 and N241 bearing a glycan A3G3F1S3 had the best diagnostic performance in distinguishing early NASH-related HCC from cirrhosis.

Fig.2 Identified N-glycoforms of serum Hp in cirrhosis and HCC.¹

At Creative Biolabs, our liquid biopsy LDT services based on glycoproteomics provide a highly promising avenue for advancing early-stage HCC detection. For further insights and detailed information, we invite you to contact us or submit an inquiry directly. Our team is ready to assist you and provide valuable guidance on this innovative approach.

Reference

1. Zhu, Jianhui, et al. "Glycopeptide biomarkers in serum haptoglobin for hepatocellular carcinoma detection in patients with nonalcoholic steatohepatitis." Journal of proteome research 19.8 (2020): 3452-3466.

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