{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T03:03:30Z","timestamp":1769828610049,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"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":["Cells"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients\u2019 clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.<\/jats:p>","DOI":"10.3390\/cells13030276","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:24:08Z","timestamp":1706865848000},"page":"276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1236-2722","authenticated-orcid":false,"given":"Samantha","family":"Epistolio","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Dazio","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Sahnane","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-1734","authenticated-orcid":false,"given":"Francesco","family":"Polinelli","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Barizzi","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9204-1410","authenticated-orcid":false,"given":"Paolo","family":"Spina","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4248-6275","authenticated-orcid":false,"given":"Federico Mattia","family":"Stefanini","sequence":"additional","affiliation":[{"name":"Department of Environmental Science and Policy, Faculty of Science and Technology-ESP, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Cerati","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Mazzucchelli","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fausto","family":"Sessa","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco Angelo","family":"Pesce","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), 6501 Bellinzona, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-3753","authenticated-orcid":false,"given":"Andrea","family":"Cardia","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-7168","authenticated-orcid":false,"given":"Francesco","family":"Marchi","sequence":"additional","affiliation":[{"name":"Service of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milo","family":"Frattini","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grochans, S., Cybulska, A.M., Simi\u0144ska, D., Korbecki, J., Kojder, K., Chlubek, D., and Baranowska-Bosiacka, I. 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