Identification of a Prognostic Microenvironment-Related Gene Signature in Glioblastoma Patients Treated with Carmustine Wafers
Despite the state-of-the-art treatment, patients diagnosed with glioblastoma (GBM) have a median overall survival (OS) of 14 months. The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contra...
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| Veröffentlicht in: | Cancers 2022-07, Vol.14 (14), p.3413 |
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| creator | Manini, Ivana Dalla, Emiliano Vendramin, Vera Cesselli, Daniela Di Loreto, Carla Skrap, Miran Ius, Tamara |
| description | Despite the state-of-the-art treatment, patients diagnosed with glioblastoma (GBM) have a median overall survival (OS) of 14 months. The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contrasting clinical results. Our retrospective evaluation of CW efficacy showed a significant improvement in terms of OS in a subgroup of patients. Given the crucial role of the tumor microenvironment (TME) in GBM progression and response to therapy, we hypothesized that the TME of patients who benefited from CW could have different properties compared to that of patients who did not show any advantage. Using an in vitro model of the glioma microenvironment, represented by glioma-associated-stem cells (GASC), we performed a transcriptomic analysis of GASC isolated from tumors of patients responsive and not responsive to CW to identify differentially expressed genes. We found different transcriptomic profiles, and we identified four genes, specifically down-regulated in GASC isolated from long-term survivors, correlated with clinical data deposited in the TCGA–GBM dataset. Our results highlight that studying the in vitro properties of patient-specific glioma microenvironments can help to identify molecular determinants potentially prognostic for patients treated with CW. |
| doi_str_mv | 10.3390/cancers14143413 |
| format | Article |
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The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contrasting clinical results. Our retrospective evaluation of CW efficacy showed a significant improvement in terms of OS in a subgroup of patients. Given the crucial role of the tumor microenvironment (TME) in GBM progression and response to therapy, we hypothesized that the TME of patients who benefited from CW could have different properties compared to that of patients who did not show any advantage. Using an in vitro model of the glioma microenvironment, represented by glioma-associated-stem cells (GASC), we performed a transcriptomic analysis of GASC isolated from tumors of patients responsive and not responsive to CW to identify differentially expressed genes. We found different transcriptomic profiles, and we identified four genes, specifically down-regulated in GASC isolated from long-term survivors, correlated with clinical data deposited in the TCGA–GBM dataset. Our results highlight that studying the in vitro properties of patient-specific glioma microenvironments can help to identify molecular determinants potentially prognostic for patients treated with CW.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14143413</identifier><identifier>PMID: 35884475</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Brain tumors ; Cancer ; Carmustine ; Drug resistance ; Drug therapy ; Gene expression ; Genetic aspects ; Glioblastoma ; Glioblastoma multiforme ; Glioma cells ; Medical prognosis ; Oncology, Experimental ; Patients ; Prognosis ; Stem cells ; Surgery ; Transcriptomics ; Tumor microenvironment ; Tumors</subject><ispartof>Cancers, 2022-07, Vol.14 (14), p.3413</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-144322282f6738f5d56a2d3766008510f614dc08561af4498032af213629e6213</citedby><cites>FETCH-LOGICAL-c465t-144322282f6738f5d56a2d3766008510f614dc08561af4498032af213629e6213</cites><orcidid>0000-0002-0562-7852 ; 0000-0002-4687-6011</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320240/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320240/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids></links><search><creatorcontrib>Manini, Ivana</creatorcontrib><creatorcontrib>Dalla, Emiliano</creatorcontrib><creatorcontrib>Vendramin, Vera</creatorcontrib><creatorcontrib>Cesselli, Daniela</creatorcontrib><creatorcontrib>Di Loreto, Carla</creatorcontrib><creatorcontrib>Skrap, Miran</creatorcontrib><creatorcontrib>Ius, Tamara</creatorcontrib><title>Identification of a Prognostic Microenvironment-Related Gene Signature in Glioblastoma Patients Treated with Carmustine Wafers</title><title>Cancers</title><description>Despite the state-of-the-art treatment, patients diagnosed with glioblastoma (GBM) have a median overall survival (OS) of 14 months. The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contrasting clinical results. Our retrospective evaluation of CW efficacy showed a significant improvement in terms of OS in a subgroup of patients. Given the crucial role of the tumor microenvironment (TME) in GBM progression and response to therapy, we hypothesized that the TME of patients who benefited from CW could have different properties compared to that of patients who did not show any advantage. Using an in vitro model of the glioma microenvironment, represented by glioma-associated-stem cells (GASC), we performed a transcriptomic analysis of GASC isolated from tumors of patients responsive and not responsive to CW to identify differentially expressed genes. We found different transcriptomic profiles, and we identified four genes, specifically down-regulated in GASC isolated from long-term survivors, correlated with clinical data deposited in the TCGA–GBM dataset. Our results highlight that studying the in vitro properties of patient-specific glioma microenvironments can help to identify molecular determinants potentially prognostic for patients treated with CW.</description><subject>Brain tumors</subject><subject>Cancer</subject><subject>Carmustine</subject><subject>Drug resistance</subject><subject>Drug therapy</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Glioblastoma</subject><subject>Glioblastoma multiforme</subject><subject>Glioma cells</subject><subject>Medical prognosis</subject><subject>Oncology, Experimental</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Stem cells</subject><subject>Surgery</subject><subject>Transcriptomics</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptks9PFTEQxxujEYKcvTbx4mWhv7a7ezEhL_okwWgA47Ep3emjZLfFtovhwt_uPCAqxM5hJu1nvjOTDiFvOTuQcmCHzkYHuXDFlVRcviC7gnWi0XpQL_-Jd8h-KVcMj5S8091rsiPbvleqa3fJ3fEIsQYfnK0hRZo8tfRbTpuYSg2OfgkuJ4g3Iac4I9mcwmQrjHQNEehZ2ERblww0RLqeQrqYbKlpRgmUQ7zQ8wz3_K9QL-nK5nlBXUz9YT32_oa88nYqsP_o98j3Tx_PV5-bk6_r49XRSeOUbmvDlZJCiF543cnet2OrrRhlpzVjfcuZ11yNDkPNrVdq6JkU1gsutRhAo98jHx50r5eLGUaHrWU7mescZptvTbLBPH2J4dJs0o0ZpGBCMRR4_yiQ088FSjVzKA6myUZISzFCDy32p5hC9N0z9CotOeJ4W0qiMS7_Uhs7gQnRJ6zrtqLmqBOSad7elz34D4U2whxciuAD3j9JOHxIwG8rJYP_MyNnZrs15tnWyN-4SbPy</recordid><startdate>20220714</startdate><enddate>20220714</enddate><creator>Manini, Ivana</creator><creator>Dalla, Emiliano</creator><creator>Vendramin, Vera</creator><creator>Cesselli, Daniela</creator><creator>Di Loreto, Carla</creator><creator>Skrap, Miran</creator><creator>Ius, Tamara</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0562-7852</orcidid><orcidid>https://orcid.org/0000-0002-4687-6011</orcidid></search><sort><creationdate>20220714</creationdate><title>Identification of a Prognostic Microenvironment-Related Gene Signature in Glioblastoma Patients Treated with Carmustine Wafers</title><author>Manini, Ivana ; 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The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contrasting clinical results. Our retrospective evaluation of CW efficacy showed a significant improvement in terms of OS in a subgroup of patients. Given the crucial role of the tumor microenvironment (TME) in GBM progression and response to therapy, we hypothesized that the TME of patients who benefited from CW could have different properties compared to that of patients who did not show any advantage. Using an in vitro model of the glioma microenvironment, represented by glioma-associated-stem cells (GASC), we performed a transcriptomic analysis of GASC isolated from tumors of patients responsive and not responsive to CW to identify differentially expressed genes. We found different transcriptomic profiles, and we identified four genes, specifically down-regulated in GASC isolated from long-term survivors, correlated with clinical data deposited in the TCGA–GBM dataset. Our results highlight that studying the in vitro properties of patient-specific glioma microenvironments can help to identify molecular determinants potentially prognostic for patients treated with CW.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>35884475</pmid><doi>10.3390/cancers14143413</doi><orcidid>https://orcid.org/0000-0002-0562-7852</orcidid><orcidid>https://orcid.org/0000-0002-4687-6011</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Brain tumors Cancer Carmustine Drug resistance Drug therapy Gene expression Genetic aspects Glioblastoma Glioblastoma multiforme Glioma cells Medical prognosis Oncology, Experimental Patients Prognosis Stem cells Surgery Transcriptomics Tumor microenvironment Tumors |
| title | Identification of a Prognostic Microenvironment-Related Gene Signature in Glioblastoma Patients Treated with Carmustine Wafers |
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