Glycoproteomics-based Liquid-biopsy LDT Development Service for Hepatocellular Carcinoma (HCC)
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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
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Specific enrichment of Fuc glycopeptides.
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High mass accuracy and high sensitivity;
Carefully chosen fragmentation methods for comprehensive characterization.
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Data analysis and interpretation
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Extensive glycan library (encompassing over 70 O-glycan and 150 N-glycan types);
High-performance search strategies;
Enhanced capability for identification of Fuc glycopeptides.
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Published data
It is urgent to develop new serum biomarkers to improve the accuracy of early diagnosis of hepatocellular carcinoma (HCC). In this study, the authors first used lectin affinity chromatography to enrich glycoproteins in serum samples of HCC patients and healthy people, and then isotope labeled these samples. Subsequently, the authors used mass spectrometry to compare the differences in glycoproteins in different serum samples. The analysis showed that 36 proteins were upregulated and 19 were downregulated in HCC patients. This showed that mass spectrometry-based quantitative glycoproteomics was an effective method that could be used to support the search for potential biomarkers for HCC.
Fig.2 Quantitative analysis of glycoproteins in serum samples.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
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Gao, Hua-Jun, et al. "Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum." Cancer Biology & Medicine 12.3 (2015): 246. Distributed under Open Access license CC BY 3.0, without modification.
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