Cargando…

Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?

Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrate...

Descripción completa

Detalles Bibliográficos
Autores principales: Foddis, Rudy, Franzini, Maria, Bonotti, Alessandra, Marino, Riccardo, Silvestri, Roberto, Fallahi, Poupak, Chiappino, Dante, Emdin, Michele, Paolicchi, Aldo, Cristaudo, Alfonso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870979/
https://www.ncbi.nlm.nih.gov/pubmed/35204402
http://dx.doi.org/10.3390/diagnostics12020311
_version_ 1784656886516154368
author Foddis, Rudy
Franzini, Maria
Bonotti, Alessandra
Marino, Riccardo
Silvestri, Roberto
Fallahi, Poupak
Chiappino, Dante
Emdin, Michele
Paolicchi, Aldo
Cristaudo, Alfonso
author_facet Foddis, Rudy
Franzini, Maria
Bonotti, Alessandra
Marino, Riccardo
Silvestri, Roberto
Fallahi, Poupak
Chiappino, Dante
Emdin, Michele
Paolicchi, Aldo
Cristaudo, Alfonso
author_sort Foddis, Rudy
collection PubMed
description Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582–0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807–0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis.
format Online
Article
Text
id pubmed-8870979
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88709792022-02-25 Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma? Foddis, Rudy Franzini, Maria Bonotti, Alessandra Marino, Riccardo Silvestri, Roberto Fallahi, Poupak Chiappino, Dante Emdin, Michele Paolicchi, Aldo Cristaudo, Alfonso Diagnostics (Basel) Article Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582–0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807–0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis. MDPI 2022-01-26 /pmc/articles/PMC8870979/ /pubmed/35204402 http://dx.doi.org/10.3390/diagnostics12020311 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Foddis, Rudy
Franzini, Maria
Bonotti, Alessandra
Marino, Riccardo
Silvestri, Roberto
Fallahi, Poupak
Chiappino, Dante
Emdin, Michele
Paolicchi, Aldo
Cristaudo, Alfonso
Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
title Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
title_full Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
title_fullStr Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
title_full_unstemmed Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
title_short Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
title_sort big and free fractions of gamma-glutamyltransferase: new diagnostic biomarkers for malignant mesothelioma?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870979/
https://www.ncbi.nlm.nih.gov/pubmed/35204402
http://dx.doi.org/10.3390/diagnostics12020311
work_keys_str_mv AT foddisrudy bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT franzinimaria bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT bonottialessandra bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT marinoriccardo bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT silvestriroberto bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT fallahipoupak bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT chiappinodante bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT emdinmichele bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT paolicchialdo bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma
AT cristaudoalfonso bigandfreefractionsofgammaglutamyltransferasenewdiagnosticbiomarkersformalignantmesothelioma