Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis
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 (<i>MGMT</i>)-methylated GB...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/3/276 |
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| author | Samantha Epistolio Giulia Dazio Ismail Zaed Nora Sahnane Debora Cipriani Francesco Polinelli Jessica Barizzi Paolo Spina Federico Mattia Stefanini Michele Cerati Sergio Balbi Luca Mazzucchelli Fausto Sessa Gianfranco Angelo Pesce Michael Reinert Andrea Cardia Francesco Marchi Milo Frattini |
| author_facet | Samantha Epistolio Giulia Dazio Ismail Zaed Nora Sahnane Debora Cipriani Francesco Polinelli Jessica Barizzi Paolo Spina Federico Mattia Stefanini Michele Cerati Sergio Balbi Luca Mazzucchelli Fausto Sessa Gianfranco Angelo Pesce Michael Reinert Andrea Cardia Francesco Marchi Milo Frattini |
| author_sort | Samantha Epistolio |
| collection | DOAJ |
| description | 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 (<i>MGMT</i>)-methylated GBM cases. However, approximately 20% of patients with <i>MGMT</i>-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 <i>IDH</i> wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients’ 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. |
| first_indexed | 2024-03-08T03:59:59Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T03:59:59Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c72d9da69f954c83934888d4eb3f37712024-02-09T15:09:51ZengMDPI AGCells2073-44092024-02-0113327610.3390/cells13030276Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme PrognosisSamantha Epistolio0Giulia Dazio1Ismail Zaed2Nora Sahnane3Debora Cipriani4Francesco Polinelli5Jessica Barizzi6Paolo Spina7Federico Mattia Stefanini8Michele Cerati9Sergio Balbi10Luca Mazzucchelli11Fausto Sessa12Gianfranco Angelo Pesce13Michael Reinert14Andrea Cardia15Francesco Marchi16Milo Frattini17Laboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, SwitzerlandLaboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, SwitzerlandService of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, SwitzerlandUnit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, ItalyService of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, SwitzerlandService of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, SwitzerlandLaboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, SwitzerlandLaboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, SwitzerlandDepartment of Environmental Science and Policy, Faculty of Science and Technology-ESP, University of Milan, 20122 Milan, ItalyUnit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, ItalyDivision of Neurological Surgery, Department of Biotechnology and Life Sciences, University of Insubria, ASST Sette Laghi, 21100 Varese, ItalyLaboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, SwitzerlandUnit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, ItalyRadiation Oncology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), 6501 Bellinzona, SwitzerlandService of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, SwitzerlandService of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, SwitzerlandService of Neurosurgery, Neurocenter of the Southern Switzerland, Regional Hospital of Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, SwitzerlandLaboratory of Genetics and Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale (EOC), 6900 Locarno, SwitzerlandGlioblastoma 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 (<i>MGMT</i>)-methylated GBM cases. However, approximately 20% of patients with <i>MGMT</i>-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 <i>IDH</i> wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients’ 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.https://www.mdpi.com/2073-4409/13/3/276glioblastomamiRNAsmiRNA pairsoverall survivalclinical outcometemozolomide |
| spellingShingle | Samantha Epistolio Giulia Dazio Ismail Zaed Nora Sahnane Debora Cipriani Francesco Polinelli Jessica Barizzi Paolo Spina Federico Mattia Stefanini Michele Cerati Sergio Balbi Luca Mazzucchelli Fausto Sessa Gianfranco Angelo Pesce Michael Reinert Andrea Cardia Francesco Marchi Milo Frattini Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis Cells glioblastoma miRNAs miRNA pairs overall survival clinical outcome temozolomide |
| title | Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis |
| title_full | Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis |
| title_fullStr | Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis |
| title_full_unstemmed | Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis |
| title_short | Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis |
| title_sort | clinical relevance and interplay between mirnas in influencing glioblastoma multiforme prognosis |
| topic | glioblastoma miRNAs miRNA pairs overall survival clinical outcome temozolomide |
| url | https://www.mdpi.com/2073-4409/13/3/276 |
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