Evaluation of the albumin‐γ‐glutamyltransferase isoenzyme as a diagnostic marker of hepatocellular carcinoma‐complicating liver cirrhosis

Pompili, Maurizio; Addolorato, Giovanni; Pignataro, Giulia; Rossi, Cristina; Zuppi, Cecilia; Covino, Marcello; Grieco, Antonio; Gasbarrini, Giovanni; Rapaccini, Gian Ludovico

doi:10.1046/j.1440-1746.2003.02962.x

Cited by 8 publications

(7 citation statements)

References 50 publications

(101 reference statements)

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“…that circulating lipoproteins are GGT carriers and that GGT is too lipophilic to circulate in a free form [26]. Furthermore, we also observed that plasma f-GGT fraction has a MW corresponding to the free GGT protein, thus demonstrating that part of plasma GGT do not require any carrier, such as lipoproteins [26] or albumin [27], to be transported in blood.…”

Section: Discussionmentioning

confidence: 50%

Gamma-Glutamyltransferase Fractions in Human Plasma and Bile: Characteristic and Biogenesis

et al. 2014

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Total plasma gamma-glutamyltransferase (GGT) activity is a sensitive, non-specific marker of liver dysfunction. Four GGT fractions (b-, m-, s-, f-GGT) were described in plasma and their differential specificity in the diagnosis of liver diseases was suggested. Nevertheless fractional GGT properties have not been investigated yet. The aim of this study was to characterize the molecular nature of fractional GGT in both human plasma and bile.Plasma was obtained from healthy volunteers; whereas bile was collected from patients undergoing liver transplantation. Molecular weight (MW), density, distribution by centrifugal sedimentation and sensitivity to both detergent (deoxycholic acid) and protease (papain) were evaluated. A partial purification of b-GGT was obtained by ultracentrifugation.Plasma b-GGT fraction showed a MW of 2000 kDa and a density between 1.063–1.210 g/ml. Detergent converted b-GGT into s-GGT, whereas papain alone did not produce any effect. Plasma m-GGT and s-GGT showed a MW of 1,000 and 200 kDa, and densities between 1.006-1.063 g/ml and 1.063–1.210 g/ml respectively. Both fractions were unaffected by deoxycholic acid, while GGT activity was recovered into f-GGT peak after papain treatment. Plasma f-GGT showed a MW of 70 kDa and a density higher than 1.21 g/ml. We identified only two chromatographic peaks, in bile, showing similar characteristics as plasma b- and f-GGT fractions.These evidences, together with centrifugal sedimentation properties and immunogold electronic microscopy data, indicate that b-GGT is constituted of membrane microvesicles in both bile and plasma, m-GGT and s-GGT might be constituted of bile-acid micelles, while f-GGT represents the free-soluble form of the enzyme.

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Section: Discussionmentioning

confidence: 50%

Gamma-Glutamyltransferase Fractions in Human Plasma and Bile: Characteristic and Biogenesis

et al. 2014

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“…A focus on these neglected enzyme groups (isomerases, transferases, and synthetases) should not only extend the spectrum using AuNPsbased enzyme assays, but also inspire the development of AuNPsbased assays for new targets. [136][137][138] Despite the benefits presented by these nano diagnostic systems, there is still a long way to go before the extensive application of colorimetric AuNPs can offer effective diagnostic tests that can be translated into the laboratory or testing near patient setting.…”

Section: Discussionmentioning

confidence: 99%

Gold nanoparticle-based colorimetric biosensors

et al. 2018

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Gold nanoparticles (AuNPs) provide excellent platforms for the development of colorimetric biosensors as they can be easily functionalised, displaying different colours depending on their size, shape and state of aggregation. In the last decade, a variety of biosensors have been developed to exploit the extent of colour changes as nano-particles (NPs) either aggregate or disperse, in the presence of analytes. Of critical importance to the design of these methods is that the behaviour of the systems has to be reproducible and predictable. Much has been accomplished in understanding the interactions between a variety of substrates and AuNPs, and how these interactions can be harnessed as colorimetric reporters in biosensors. However, despite these developments, only a few biosensors have been used in practice for the detection of analytes in biological samples. The transition from proof of concept to market biosensors requires extensive long-term reliability and shelf life testing, and modification of protocols and design features to make them safe and easy to use by the population at large. Developments in the next decade will see the adoption of user friendly biosensors for point-of-care and medical diagnosis as innovations are brought to improve the analytical performances and usability of the current designs. This review discusses the mechanisms, strategies, recent advances and perspectives for the use of AuNPs as colorimetric biosensors.

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“…5 Nevertheless, serum AFP is not particularly efficient in detecting HCC at early stages, and its specificity is often shadowed by high false positive signals from patients with other liver-related diseases such as viral hepatitis and cirrhosis. 6 In this regard, several groups have recently suggested several soluble tumor markers such as glypican-3, 7 γ-glutamyltransferase II, 8 des-γ-carboxypro thrombin, 9 lens culinaris agglutinin-reactive AFP 10 and α1-antitrypsin, 11 that may improve the detection rate for early HCC. Nevertheless, their clinical utilities remain to be further determined in multicenter clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Expression Signature Distinguishes Cancerous and Nonmalignant Tissues in Hepatocellular Carcinoma

et al. 2009

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Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and non-malignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent non-tumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n=55) and validation (n=25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5% respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak’s score. The described model using biomarker signatures could accurately distinguish HCC from non-malignant tissues, which may also provide hints and guidance on how normal hepatocytes are transformed to malignant state during tumor progression.

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Evaluation of the albumin‐γ‐glutamyltransferase isoenzyme as a diagnostic marker of hepatocellular carcinoma‐complicating liver cirrhosis

Abstract: Albumin-gamma-glutamyltransferase appears to be a sensitive diagnostic marker of both advanced and small hepatocellular carcinoma-complicating liver cirrhosis.

Cited by 8 publications

References 50 publications

Gamma-Glutamyltransferase Fractions in Human Plasma and Bile: Characteristic and Biogenesis

Gamma-Glutamyltransferase Fractions in Human Plasma and Bile: Characteristic and Biogenesis

Gold nanoparticle-based colorimetric biosensors

Proteomic Expression Signature Distinguishes Cancerous and Nonmalignant Tissues in Hepatocellular Carcinoma

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