{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:45:25Z","timestamp":1768268725893,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007514","name":"University of Pisa","doi-asserted-by":"publisher","award":["PRA 2017"],"award-info":[{"award-number":["PRA 2017"]}],"id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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\u20130.777). 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\u20130.943, p = &lt;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.<\/jats:p>","DOI":"10.3390\/diagnostics12020311","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T11:02:53Z","timestamp":1643194973000},"page":"311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1330-3863","authenticated-orcid":false,"given":"Rudy","family":"Foddis","sequence":"first","affiliation":[{"name":"Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-9370","authenticated-orcid":false,"given":"Maria","family":"Franzini","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Bonotti","sequence":"additional","affiliation":[{"name":"Preventive and Occupational Medicine, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-5235","authenticated-orcid":false,"given":"Roberto","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Preventive and Occupational Medicine, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poupak","family":"Fallahi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante","family":"Chiappino","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione CNR Regione Toscana \u201cG. Monasterio\u201d, 54100 Massa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Division, Fondazione Toscana \u201cG. Monasterio\u201d, 56124 Pisa, Italy"},{"name":"Institute of Life Sciences, Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldo","family":"Paolicchi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Cristaudo","sequence":"additional","affiliation":[{"name":"Preventive and Occupational Medicine, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1183\/09059180.00007014","article-title":"Malignant pleural mesothelioma: History, controversy and future of a manmade epidemic","volume":"24","author":"Stella","year":"2015","journal-title":"Eur. 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