Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients

Treatment failures of glioblastoma (GBM) occur within high-dose radiation fields. We hypothesized that this is due to increased capacity for DNA damage repair in GBM. We identified 24 adult GBM patients treated with maximal safe resection followed by radiation with concurrent and adjuvant temozolomi...

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Autores principales:	Christopher Morrison, Eric Weterings, Daruka Mahadevan, Abhay Sanan, Martin Weinand, Baldassarre Stea
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	RAD51 GBM NanoString nCounter gene expression prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0cf783fad81443e0916542cf070d7c6e
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spelling	oai:doaj.org-article:0cf783fad81443e0916542cf070d7c6e2021-11-11T15:28:58ZExpression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients10.3390/cancers132153582072-6694https://doaj.org/article/0cf783fad81443e0916542cf070d7c6e2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5358https://doaj.org/toc/2072-6694Treatment failures of glioblastoma (GBM) occur within high-dose radiation fields. We hypothesized that this is due to increased capacity for DNA damage repair in GBM. We identified 24 adult GBM patients treated with maximal safe resection followed by radiation with concurrent and adjuvant temozolomide. The mRNA from patients was quantified using NanoString Technologies’ nCounter platform and compared with 12 non-neoplastic temporal lobe tissue samples as a control. Differential expression analysis identified seven DNA repair genes significantly upregulated in GBM tissues relative to controls (>4-fold difference, adjusted <i>p</i> values < 0.001). Among these seven genes, Cox proportional hazards models identified RAD51 to be associated with an increased risk of death (HR = 3.49; <i>p</i> = 0.03). Kaplan–Meier (KM) analysis showed that patients with high RAD51 expression had significantly shorter OS compared to low levels (median OS of 10.6 mo. vs 20.1 mo.; log-rank <i>p</i> = 0.03). Our findings were validated in a larger external dataset of 162 patients using publicly available gene expression data quantified by the same NanoString technology (median OS of 13.8 mo. vs. 17.4 mo; log-rank <i>p</i> = 0.006). Within this uniformly treated GBM population, RAD51, in the homologous recombination pathway, was overexpressed (vs. normal brain) and inversely correlated with OS. High RAD51 expression may be a prognostic biomarker and a therapeutic target in GBM.Christopher MorrisonEric WeteringsDaruka MahadevanAbhay SananMartin WeinandBaldassarre SteaMDPI AGarticleRAD51GBMNanoString nCountergene expressionprognostic markerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5358, p 5358 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RAD51 GBM NanoString nCounter gene expression prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	RAD51 GBM NanoString nCounter gene expression prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Christopher Morrison Eric Weterings Daruka Mahadevan Abhay Sanan Martin Weinand Baldassarre Stea Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
description	Treatment failures of glioblastoma (GBM) occur within high-dose radiation fields. We hypothesized that this is due to increased capacity for DNA damage repair in GBM. We identified 24 adult GBM patients treated with maximal safe resection followed by radiation with concurrent and adjuvant temozolomide. The mRNA from patients was quantified using NanoString Technologies’ nCounter platform and compared with 12 non-neoplastic temporal lobe tissue samples as a control. Differential expression analysis identified seven DNA repair genes significantly upregulated in GBM tissues relative to controls (>4-fold difference, adjusted <i>p</i> values < 0.001). Among these seven genes, Cox proportional hazards models identified RAD51 to be associated with an increased risk of death (HR = 3.49; <i>p</i> = 0.03). Kaplan–Meier (KM) analysis showed that patients with high RAD51 expression had significantly shorter OS compared to low levels (median OS of 10.6 mo. vs 20.1 mo.; log-rank <i>p</i> = 0.03). Our findings were validated in a larger external dataset of 162 patients using publicly available gene expression data quantified by the same NanoString technology (median OS of 13.8 mo. vs. 17.4 mo; log-rank <i>p</i> = 0.006). Within this uniformly treated GBM population, RAD51, in the homologous recombination pathway, was overexpressed (vs. normal brain) and inversely correlated with OS. High RAD51 expression may be a prognostic biomarker and a therapeutic target in GBM.
format	article
author	Christopher Morrison Eric Weterings Daruka Mahadevan Abhay Sanan Martin Weinand Baldassarre Stea
author_facet	Christopher Morrison Eric Weterings Daruka Mahadevan Abhay Sanan Martin Weinand Baldassarre Stea
author_sort	Christopher Morrison
title	Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
title_short	Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
title_full	Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
title_fullStr	Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
title_full_unstemmed	Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
title_sort	expression levels of rad51 inversely correlate with survival of glioblastoma patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0cf783fad81443e0916542cf070d7c6e
work_keys_str_mv	AT christophermorrison expressionlevelsofrad51inverselycorrelatewithsurvivalofglioblastomapatients AT ericweterings expressionlevelsofrad51inverselycorrelatewithsurvivalofglioblastomapatients AT darukamahadevan expressionlevelsofrad51inverselycorrelatewithsurvivalofglioblastomapatients AT abhaysanan expressionlevelsofrad51inverselycorrelatewithsurvivalofglioblastomapatients AT martinweinand expressionlevelsofrad51inverselycorrelatewithsurvivalofglioblastomapatients AT baldassarrestea expressionlevelsofrad51inverselycorrelatewithsurvivalofglioblastomapatients
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Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients

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