Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer

Abstract SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Katharina Leitner, Irina Tsibulak, Verena Wieser, Katharina Knoll, Daniel Reimer, Christian Marth, Heidi Fiegl, Alain G. Zeimet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c0f898d9b817455c806a36660ea6347a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c0f898d9b817455c806a36660ea6347a
record_format	dspace
spelling	oai:doaj.org-article:c0f898d9b817455c806a36660ea6347a2021-12-02T11:40:41ZClinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer10.1038/s41598-020-77532-x2045-2322https://doaj.org/article/c0f898d9b817455c806a36660ea6347a2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77532-xhttps://doaj.org/toc/2045-2322Abstract SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients’ outcome. Optimal thresholds for high and low expression of both variables were calculated by the Youden’s index based on receiver operating characteristic (ROC) curves. High SMARCA4 mRNA expression was independently associated with favorable progression-free survival (PFS) (P = 0.03) and overall survival (OS) (P = 0.018). As Youden’s threshold determination for EZH2 yielded a S-shaped ROC-curve, two cut-off points (29th and 94th percentile) predicting opposite features were defined. Whereas EZH2 mRNA levels beyond the 29th percentile independently predicted poor PFS (P = 0.034), Cox-regression in EZH2 transcripts above the 94th percentile revealed a conversion from unfavorable to favorable PFS and OS (P = 0.009 and P = 0.032, respectively). High SMARCA4 expression associates with improved survival, whereas moderate/high EZH2 expression predicts poor outcome, which converts to favorable survival in ultra-high expressing OCs. This small OC subgroup could be characterized by REV7-abrogated platinum hypersensitivity but concomitant PARP-inhibitor resistance.Katharina LeitnerIrina TsibulakVerena WieserKatharina KnollDaniel ReimerChristian MarthHeidi FieglAlain G. ZeimetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katharina Leitner Irina Tsibulak Verena Wieser Katharina Knoll Daniel Reimer Christian Marth Heidi Fiegl Alain G. Zeimet Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer
description	Abstract SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients’ outcome. Optimal thresholds for high and low expression of both variables were calculated by the Youden’s index based on receiver operating characteristic (ROC) curves. High SMARCA4 mRNA expression was independently associated with favorable progression-free survival (PFS) (P = 0.03) and overall survival (OS) (P = 0.018). As Youden’s threshold determination for EZH2 yielded a S-shaped ROC-curve, two cut-off points (29th and 94th percentile) predicting opposite features were defined. Whereas EZH2 mRNA levels beyond the 29th percentile independently predicted poor PFS (P = 0.034), Cox-regression in EZH2 transcripts above the 94th percentile revealed a conversion from unfavorable to favorable PFS and OS (P = 0.009 and P = 0.032, respectively). High SMARCA4 expression associates with improved survival, whereas moderate/high EZH2 expression predicts poor outcome, which converts to favorable survival in ultra-high expressing OCs. This small OC subgroup could be characterized by REV7-abrogated platinum hypersensitivity but concomitant PARP-inhibitor resistance.
format	article
author	Katharina Leitner Irina Tsibulak Verena Wieser Katharina Knoll Daniel Reimer Christian Marth Heidi Fiegl Alain G. Zeimet
author_facet	Katharina Leitner Irina Tsibulak Verena Wieser Katharina Knoll Daniel Reimer Christian Marth Heidi Fiegl Alain G. Zeimet
author_sort	Katharina Leitner
title	Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer
title_short	Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer
title_full	Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer
title_fullStr	Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer
title_full_unstemmed	Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer
title_sort	clinical impact of ezh2 and its antagonist smarca4 in ovarian cancer
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/c0f898d9b817455c806a36660ea6347a
work_keys_str_mv	AT katharinaleitner clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT irinatsibulak clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT verenawieser clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT katharinaknoll clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT danielreimer clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT christianmarth clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT heidifiegl clinicalimpactofezh2anditsantagonistsmarca4inovariancancer AT alaingzeimet clinicalimpactofezh2anditsantagonistsmarca4inovariancancer
_version_	1718395603406290944

Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer

Ejemplares similares