{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:38:15Z","timestamp":1780987095956,"version":"3.54.1"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Ticinese contro il Cancro"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) remains one of the tumors with the worst prognosis. In recent years, a better overall survival (OS) has been described in cases subjected to Gross Total Resection (GTR) that were presenting hypermethylation of Methylguanine-DNA methyltransferase (MGMT) promoter. Recently, also the expression of specific miRNAs involved in MGMT silencing has been related to survival. In this study, we evaluate MGMT expression by immunohistochemistry (IHC), MGMT promoter methylation and miRNA expression in 112 GBMs and correlate the data to patients\u2019 clinical outcomes. Statistical analyses demonstrate a significant association between positive MGMT IHC and the expression of miR-181c, miR-195, miR-648 and miR-767.3p between unmethylated cases and the low expression of miR-181d and miR-648 and between methylated cases and the low expression of miR-196b. Addressing the concerns of clinical associations, a better OS has been described in presence of negative MGMT IHC, in methylated patients and in the cases with miR-21, miR-196b overexpression or miR-767.3 downregulation. In addition, a better progression-free survival (PFS) is associated with MGMT methylation and GTR but not with MGMT IHC and miRNA expression. In conclusion, our data reinforce the clinical relevance of miRNA expression as an additional marker to predict efficacy of chemoradiation in GBM.<\/jats:p>","DOI":"10.3390\/jcm12052061","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:22:05Z","timestamp":1678072925000},"page":"2061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of MGMT Downregulation Induced by miRNA in Glioblastoma and Possible Effect on Temozolomide Sensitivity"],"prefix":"10.3390","volume":"12","author":[{"given":"Andrea","family":"Cardia","sequence":"first","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1236-2722","authenticated-orcid":false,"given":"Samantha","family":"Epistolio","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Zaed","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Sahnane","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Cerutti","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Cipriani","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Barizzi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Spina","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4248-6275","authenticated-orcid":false,"given":"Federico Mattia","family":"Stefanini","sequence":"additional","affiliation":[{"name":"Department of Enviromental Science and Policy, Faculty of Science and Technology-ESP, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cerati","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Balbi","sequence":"additional","affiliation":[{"name":"Division of Neurological Surgery, Department of Biotechnology and Life Sciences, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mazzucchelli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Sessa","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco Angelo","family":"Pesce","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), 6501 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0971-9543","authenticated-orcid":false,"given":"Michael","family":"Reinert","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"},{"name":"Faculty of Medicine, University of the Southern Switzerland, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milo","family":"Frattini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marchi","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero 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