Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer

Abstract In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen trea...

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Autores principales: Tommaso De Marchi, Mieke A. Timmermans, Anieta M. Sieuwerts, Marcel Smid, Maxime P. Look, Nicolai Grebenchtchikov, Fred C. G. J. Sweep, Jan G. Smits, Viktor Magdolen, Carolien H. M. van Deurzen, John A. Foekens, Arzu Umar, John W. Martens
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:dbc96afce5a543d8b843426a5e4e8e642021-12-02T11:53:05ZPhosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer10.1038/s41598-017-02296-w2045-2322https://doaj.org/article/dbc96afce5a543d8b843426a5e4e8e642017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02296-whttps://doaj.org/toc/2045-2322Abstract In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal therapy naïve primary breast carcinomas was immunohistochemically (IHC) stained for PSAT1. Staining was analyzed for association with patient’s time to progression (TTP) and overall response on first-line tamoxifen for recurrent disease. PSAT1 mRNA levels were also assessed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR; n = 161) and Affymetrix GeneChip (n = 155). Association of PSAT1 to biological pathways on tamoxifen outcome were assessed by global test. PSAT1 protein and mRNA levels were significantly associated to poor outcome to tamoxifen treatment. When comparing PSAT1 protein and mRNA levels, IHC and RT-qPCR data showed a significant association. Global test results showed that cytokine and JAK-STAT signaling were associated to PSAT1 expression. We hereby report that PSAT1 protein and mRNA levels measured in ER positive primary tumors are associated with poor clinical outcome to tamoxifen.Tommaso De MarchiMieke A. TimmermansAnieta M. SieuwertsMarcel SmidMaxime P. LookNicolai GrebenchtchikovFred C. G. J. SweepJan G. SmitsViktor MagdolenCarolien H. M. van DeurzenJohn A. FoekensArzu UmarJohn W. MartensNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tommaso De Marchi
Mieke A. Timmermans
Anieta M. Sieuwerts
Marcel Smid
Maxime P. Look
Nicolai Grebenchtchikov
Fred C. G. J. Sweep
Jan G. Smits
Viktor Magdolen
Carolien H. M. van Deurzen
John A. Foekens
Arzu Umar
John W. Martens
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
description Abstract In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal therapy naïve primary breast carcinomas was immunohistochemically (IHC) stained for PSAT1. Staining was analyzed for association with patient’s time to progression (TTP) and overall response on first-line tamoxifen for recurrent disease. PSAT1 mRNA levels were also assessed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR; n = 161) and Affymetrix GeneChip (n = 155). Association of PSAT1 to biological pathways on tamoxifen outcome were assessed by global test. PSAT1 protein and mRNA levels were significantly associated to poor outcome to tamoxifen treatment. When comparing PSAT1 protein and mRNA levels, IHC and RT-qPCR data showed a significant association. Global test results showed that cytokine and JAK-STAT signaling were associated to PSAT1 expression. We hereby report that PSAT1 protein and mRNA levels measured in ER positive primary tumors are associated with poor clinical outcome to tamoxifen.
format article
author Tommaso De Marchi
Mieke A. Timmermans
Anieta M. Sieuwerts
Marcel Smid
Maxime P. Look
Nicolai Grebenchtchikov
Fred C. G. J. Sweep
Jan G. Smits
Viktor Magdolen
Carolien H. M. van Deurzen
John A. Foekens
Arzu Umar
John W. Martens
author_facet Tommaso De Marchi
Mieke A. Timmermans
Anieta M. Sieuwerts
Marcel Smid
Maxime P. Look
Nicolai Grebenchtchikov
Fred C. G. J. Sweep
Jan G. Smits
Viktor Magdolen
Carolien H. M. van Deurzen
John A. Foekens
Arzu Umar
John W. Martens
author_sort Tommaso De Marchi
title Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
title_short Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
title_full Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
title_fullStr Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
title_full_unstemmed Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
title_sort phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/dbc96afce5a543d8b843426a5e4e8e64
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