Evaluation of AGP Fucosylation as a Marker for Hepatocellular Carcinoma of Three Different Etiologies

Liang, Jing; Zhu, Jianhui; Wang, Mengmeng; Singal, Amit G.; Odewole, Mobolaji; Kagan, Sofia; Renteria, Veronica; Liu, Suyu; Parikh, Neehar D.; Lubman, David M.

doi:10.1038/s41598-019-48043-1

Cited by 25 publications

(13 citation statements)

References 39 publications

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“…Alpha-1 acid glycoprotein (AGP) is an acute-phase glycoprotein synthesized mainly by hepatocytes and has different glycoforms dependent on the pathophysiological conditions (152), and multifucosylated AGP can be used as a novel biomarker for HCC (153). Liang et al (154) found the trifucosylated N-glycan of AGP presented in HCC patients but absent in healthy controls and most cirrhosis patients and could differentiate HCC from cirrhosis with AUROCs of 0.707-0.751 in various causes of liver diseases and exhibited an AUROC of 0.709, sensitivity of 52%, and specificity of 80% for differentiating ANHC from LC. These results suggest that the AGP could serve as a potential marker for diagnosing HCC, including ANHC.…”

Section: Agpmentioning

confidence: 99%

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

2020

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An early diagnosis of hepatocellular carcinoma (HCC) followed by effective treatment is currently critical for improving the prognosis and reducing the associated economic burden. Alpha-fetoprotein (AFP) is the most widely used biomarker for HCC diagnosis. Based on elevated serum AFP levels as well as typical imaging features, AFP-positive HCC (APHC) can be easily diagnosed, but AFP-negative HCC (ANHC) is not easily detected due to lack of ideal biomarkers and thus mainly reliance on imaging. Imaging for the diagnosis of ANHC is probably insufficient in sensitivity and/or specificity because most ANHC tumors are small and early-stage HCC, and it is involved in sophisticated techniques and high costs. Moreover, ANHC accounts for nearly half of HCC and exhibits a better prognosis compared with APHC. Therefore, the diagnosis of ANHC in clinical practice has been a critical issue for the early treatment and prognosis improvement of HCC. In recent years, tremendous efforts have been made to discover new biomarkers complementary to AFP for HCC diagnosis. In this review, we systematically review and discuss the recent advances of blood biomarkers for HCC diagnosis, including DNA biomarkers, RNA biomarkers, protein biomarkers, and conventional laboratory metrics, focusing on their diagnostic evaluation alone and in combination, in particular on their diagnostic performance for ANHC.

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Section: Agpmentioning

confidence: 99%

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

2020

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“…In related work, Liang et al applied MALDI‐MS glycan profiling to AGP from serum where AGP was isolated with a chemical precipitation method. The AGP glycan profile was more complex than Hp, and yielded nine peaks in the MALDI MS spectrum.…”

Section: Discovery—mass Spectrometry‐based Assaysmentioning

confidence: 99%

Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Zhu¹,

Warner²,

Parikh³

et al. 2018

Mass Spectrometry Reviews

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Hepatocellular carcinoma (HCC) is the third most‐common cause of cancer‐related death worldwide. Most cases of HCC develop in patients that already have liver cirrhosis and have been recommended for surveillance for an early onset of HCC. Cirrhosis is the final common pathway for several etiologies of liver disease, including hepatitis B and C, alcohol, and increasingly non‐alcoholic fatty liver disease. Only 20–30% of patients with HCC are eligible for curative therapy due primarily to inadequate early‐detection strategies. Reliable, accurate biomarkers for HCC early detection provide the highest likelihood of curative therapy and survival; however, current early‐detection methods that use abdominal ultrasound and serum alpha fetoprotein are inadequate due to poor adherence and limited sensitivity and specificity. There is an urgent need for convenient and highly accurate validated biomarkers for HCC early detection. The theme of this review is the development of new methods to discover glycoprotein‐based markers for detection of HCC with mass spectrometry approaches. We outline the non‐mass spectrometry based methods that have been used to discover HCC markers including immunoassays, capillary electrophoresis, 2‐D gel electrophoresis, and lectin‐FLISA assays. We describe the development and results of mass spectrometry‐based assays for glycan screening based on either MALDI‐MS or ESI analysis. These analyses might be based on the glycan content of serum or on glycan screening for target molecules from serum. We describe some of the specific markers that have been developed as a result, including for proteins such as Haptoglobin, Hemopexin, Kininogen, and others. We discuss the potential role for other technologies, including PGC chromatography and ion mobility, to separate isoforms of glycan markers. Analyses of glycopeptides based on new technologies and innovative softwares are described and also their potential role in discovery of markers of HCC. These technologies include new fragmentation methods such as EThcD and stepped HCD, which can identify large numbers of glycopeptide structures from serum. The key role of lectin extraction in various assays for intact glycopeptides or their truncated versions is also described, where various core‐fucosylated and hyperfucosylated glycopeptides have been identified as potential markers of HCC. Finally, we describe the role of LC‐MRMs or lectin‐FLISA MRMs as a means to validate these glycoprotein markers from patient samples. These technological advancements in mass spectrometry have the potential to lead to novel biomarkers to improve the early detection of HCC.

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“…AGP glycosylation pattern is rather complex and heterogeneous [reviewed in detail by Fournier et al (2000) ; and further studied by Fernandes et al, 2015 ]. Multiple glycan combinations have been detected in the plasma of healthy humans ( Treuheit et al, 1992 ; Ongay and Neususs, 2010 ; Baerenfaenger and Meyer, 2018 ; Keser et al, 2021 ) and changes under pathological states have been reported ( De Graaf et al, 1993 ; Liang et al, 2019 ; Keser et al, 2021 ). More specifically, branches with sialic acid are also fucosilated creating highly biologically active sialyl-Lewis X epitopes (sLe x ).…”

Section: Agp Definition and Molecular Characteristicsmentioning

confidence: 99%

Into the Labyrinth of the Lipocalin α1-Acid Glycoprotein

Ruiz

2021

Front. Physiol.

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α1-acid glycoprotein (AGP), also known as Orosomucoid (ORM), belongs to the Lipocalin protein family and it is well-known for being a positive acute-phase protein. AGP is mostly found in plasma, with the liver as main contributor, but it is also expressed in other tissues such as the brain or the adipose tissue. Despite the vast literature on AGP, the physiological functions of the protein remain to be elucidated. A large number of activities mostly related to protection and immune system modulation have been described. Recently created AGP-knockout models have suggested novel physiological roles of AGP, including regulation of metabolism. AGP has an outstanding ability to efficiently bind endogenous and exogenous small molecules that together with the complex and variable glycosylation patterns, determine AGP functions. This review summarizes and discusses the recent findings on AGP structure (including glycans), ligand-binding ability, regulation, and physiological functions of AGP. Moreover, this review explores possible molecular and functional connections between AGP and other members of the Lipocalin protein family.

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Evaluation of AGP Fucosylation as a Marker for Hepatocellular Carcinoma of Three Different Etiologies

Cited by 25 publications

References 39 publications

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Into the Labyrinth of the Lipocalin α1-Acid Glycoprotein

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