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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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. M. Martens
External organisations
  • Erasmus University Medical Center
Research areas and keywords

Keywords

  • Journal Article
Original languageEnglish
Article number2099
JournalScientific Reports
Volume7
Issue number1
Publication statusPublished - 2017 May 18
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes