Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)

Abstract O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated met...

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Autores principales:	Arshad A. Pandith, Iqbal Qasim, Wani Zahoor, Parveen Shah, Abdul R. Bhat, Dheera Sanadhya, Zafar A. Shah, Niyaz A. Naikoo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/548c0cac4dd5430d8f1be989d8f19c25
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spelling	oai:doaj.org-article:548c0cac4dd5430d8f1be989d8f19c252021-12-02T11:41:25ZConcordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)10.1038/s41598-018-25169-22045-2322https://doaj.org/article/548c0cac4dd5430d8f1be989d8f19c252018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25169-2https://doaj.org/toc/2045-2322Abstract O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.Arshad A. PandithIqbal QasimWani ZahoorParveen ShahAbdul R. BhatDheera SanadhyaZafar A. ShahNiyaz A. NaikooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arshad A. Pandith Iqbal Qasim Wani Zahoor Parveen Shah Abdul R. Bhat Dheera Sanadhya Zafar A. Shah Niyaz A. Naikoo Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)
description	Abstract O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.
format	article
author	Arshad A. Pandith Iqbal Qasim Wani Zahoor Parveen Shah Abdul R. Bhat Dheera Sanadhya Zafar A. Shah Niyaz A. Naikoo
author_facet	Arshad A. Pandith Iqbal Qasim Wani Zahoor Parveen Shah Abdul R. Bhat Dheera Sanadhya Zafar A. Shah Niyaz A. Naikoo
author_sort	Arshad A. Pandith
title	Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)
title_short	Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)
title_full	Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)
title_fullStr	Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)
title_full_unstemmed	Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)
title_sort	concordant association validates mgmt methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (temozolomide)
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/548c0cac4dd5430d8f1be989d8f19c25
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Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide)

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