Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era
Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. Patients wit...
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| Veröffentlicht in: | PloS one 2012-03, Vol.7 (3), p.e33684 |
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| creator | Carico, Christine Nuño, Miriam Mukherjee, Debraj Elramsisy, Adam Dantis, Jocelynn Hu, Jethro Rudnick, Jeremy Yu, John S Black, Keith L Bannykh, Serguei I Patil, Chirag G |
| description | Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed.
Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival.
Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p = .71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p = .01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p = .04), low KPS (HR 3.57, CI: 2.20-5.79, p |
| doi_str_mv | 10.1371/journal.pone.0033684 |
| format | Article |
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Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival.
Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p = .71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p = .01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p = .04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p = .22).
Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0033684</identifier><identifier>PMID: 22479427</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adolescent ; Adult ; Age ; Aged ; Aged, 80 and over ; AKT protein ; Analysis ; Antineoplastic Agents, Alkylating - therapeutic use ; Biology ; Biopsy ; Brain cancer ; Cancer ; Care and treatment ; Cell cycle ; Cytokines ; Dacarbazine - analogs & derivatives ; Dacarbazine - therapeutic use ; Epidermal growth factor ; Epidermal growth factor receptors ; Female ; Gene expression ; Glioblastoma ; Glioblastoma - drug therapy ; Glioblastoma - metabolism ; Glioblastoma - mortality ; Glioblastomas ; Hazards ; Humans ; Identification methods ; Kinases ; Male ; Medical diagnosis ; Medical research ; Medicine ; Melanoma ; Middle Aged ; Mortality ; Multivariate analysis ; Mutation ; Neurosurgery ; Patient outcomes ; Patients ; Phosphatidylinositol 3-Kinases - metabolism ; Physicians ; Prognosis ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Radiation ; Regulators ; Retrospective Studies ; Signal Transduction ; Surgery ; Survival ; Survival Analysis ; Temozolomide ; Tumor suppressor genes ; Tumorigenesis ; Young Adult</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e33684</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Carico et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Carico et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-c8a4011e82a6e20ec164002b68a199e5771fdab4b3028eba5fe20f47729870173</citedby><cites>FETCH-LOGICAL-c691t-c8a4011e82a6e20ec164002b68a199e5771fdab4b3028eba5fe20f47729870173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315579/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315579/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22479427$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carico, Christine</creatorcontrib><creatorcontrib>Nuño, Miriam</creatorcontrib><creatorcontrib>Mukherjee, Debraj</creatorcontrib><creatorcontrib>Elramsisy, Adam</creatorcontrib><creatorcontrib>Dantis, Jocelynn</creatorcontrib><creatorcontrib>Hu, Jethro</creatorcontrib><creatorcontrib>Rudnick, Jeremy</creatorcontrib><creatorcontrib>Yu, John S</creatorcontrib><creatorcontrib>Black, Keith L</creatorcontrib><creatorcontrib>Bannykh, Serguei I</creatorcontrib><creatorcontrib>Patil, Chirag G</creatorcontrib><title>Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed.
Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival.
Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p = .71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p = .01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p = .04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p = .22).
Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Biology</subject><subject>Biopsy</subject><subject>Brain cancer</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cytokines</subject><subject>Dacarbazine - analogs & derivatives</subject><subject>Dacarbazine - therapeutic use</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glioblastoma</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - mortality</subject><subject>Glioblastomas</subject><subject>Hazards</subject><subject>Humans</subject><subject>Identification methods</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Neurosurgery</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Physicians</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Radiation</subject><subject>Regulators</subject><subject>Retrospective Studies</subject><subject>Signal Transduction</subject><subject>Surgery</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Temozolomide</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><subject>Young 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metabolism</topic><topic>Physicians</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>Radiation</topic><topic>Regulators</topic><topic>Retrospective Studies</topic><topic>Signal Transduction</topic><topic>Surgery</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Temozolomide</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenesis</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carico, Christine</creatorcontrib><creatorcontrib>Nuño, Miriam</creatorcontrib><creatorcontrib>Mukherjee, Debraj</creatorcontrib><creatorcontrib>Elramsisy, Adam</creatorcontrib><creatorcontrib>Dantis, Jocelynn</creatorcontrib><creatorcontrib>Hu, Jethro</creatorcontrib><creatorcontrib>Rudnick, Jeremy</creatorcontrib><creatorcontrib>Yu, John 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Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carico, Christine</au><au>Nuño, Miriam</au><au>Mukherjee, Debraj</au><au>Elramsisy, Adam</au><au>Dantis, Jocelynn</au><au>Hu, Jethro</au><au>Rudnick, Jeremy</au><au>Yu, John S</au><au>Black, Keith L</au><au>Bannykh, Serguei I</au><au>Patil, Chirag G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-03-29</date><risdate>2012</risdate><volume>7</volume><issue>3</issue><spage>e33684</spage><pages>e33684-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed.
Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival.
Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5). Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (p = .71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, p = .01). Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p = .04), low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p = .22).
Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22479427</pmid><doi>10.1371/journal.pone.0033684</doi><tpages>e33684</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-03, Vol.7 (3), p.e33684 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324393885 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 1-Phosphatidylinositol 3-kinase Adolescent Adult Age Aged Aged, 80 and over AKT protein Analysis Antineoplastic Agents, Alkylating - therapeutic use Biology Biopsy Brain cancer Cancer Care and treatment Cell cycle Cytokines Dacarbazine - analogs & derivatives Dacarbazine - therapeutic use Epidermal growth factor Epidermal growth factor receptors Female Gene expression Glioblastoma Glioblastoma - drug therapy Glioblastoma - metabolism Glioblastoma - mortality Glioblastomas Hazards Humans Identification methods Kinases Male Medical diagnosis Medical research Medicine Melanoma Middle Aged Mortality Multivariate analysis Mutation Neurosurgery Patient outcomes Patients Phosphatidylinositol 3-Kinases - metabolism Physicians Prognosis Proteins Proto-Oncogene Proteins c-akt - metabolism PTEN Phosphohydrolase - metabolism PTEN protein Radiation Regulators Retrospective Studies Signal Transduction Surgery Survival Survival Analysis Temozolomide Tumor suppressor genes Tumorigenesis Young Adult |
| title | Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T05%3A00%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Loss%20of%20PTEN%20is%20not%20associated%20with%20poor%20survival%20in%20newly%20diagnosed%20glioblastoma%20patients%20of%20the%20temozolomide%20era&rft.jtitle=PloS%20one&rft.au=Carico,%20Christine&rft.date=2012-03-29&rft.volume=7&rft.issue=3&rft.spage=e33684&rft.pages=e33684-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0033684&rft_dat=%3Cgale_plos_%3EA477004211%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1324393885&rft_id=info:pmid/22479427&rft_galeid=A477004211&rft_doaj_id=oai_doaj_org_article_7ff0af6fb2614a7da8717a35022002d8&rfr_iscdi=true |