Shreeya Kotecha
Dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression
Kotecha, Shreeya; Lebot, Marie N.; Sukkarn, Bhudsaban; Ball, Graham; Moseley, Paul M.; Chan, Stephen Y.; Green, Andrew R.; Rakha, Emad; Ellis, Ian O.; Martin, Stewart G.; Storr, Sarah J.
Authors
Marie N. Lebot
Bhudsaban Sukkarn
Graham Ball
Paul M. Moseley
Stephen Y. Chan
ANDREW GREEN ANDREW.GREEN@NOTTINGHAM.AC.UK
Associate Professor
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology
SARAH STORR sarah.storr@nottingham.ac.uk
Assistant Professor
Abstract
Dopamine and cAMP regulated phosphoprotein 32?kDa (DARPP-32) also known as phosphoprotein phosphatase-1 regulatory subunit 1B and encoded by the PPP1R1B gene is an inhibitor of protein phosphatase-1 and protein kinase A. DARPP-32 is expressed in a wide range of epithelial cells and some solid tumours; however, its role in breast cancer is only partially defined. DARPP-32 expression was determined using immunohistochemistry in two independent cohorts of early stage invasive breast cancer patients (discovery n?=?1352; validation n?=?1655), and 112 HER2 positive breast cancer patients treated with trastuzumab and adjuvant chemotherapy. PPP1R1B mRNA expression was assessed in the METABRIC cohort (n?=?1980), using artificial neural network analysis to identify associated genes. In the discovery cohort, low nuclear expression of DARPP-32 was significantly associated with shorter survival (P?=?0.041), which was independent of other prognostic variables (P?=?0.019). In the validation cohort, low cytoplasmic and nuclear expression was significantly associated with shorter survival (both P?=?0.002), with cytoplasmic expression independent of other prognostic variables (P?=?0.023). Stronger associations with survival in oestrogen receptor (ER) positive disease were observed. In patients treated with trastuzumab, low nuclear expression was significantly associated with adverse progression-free survival (P?=?0.031). In the METABRIC cohort, low PPP1R1B expression was associated with shortened survival of ER positive patients. Expression of CDC42 and GRB7, amongst others, were associated with PPP1R1B expression. This data suggests a role for DARPP-32 as a prognostic marker with clinical utility in breast cancer.
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 21, 2019 |
Online Publication Date | Nov 18, 2019 |
Publication Date | Nov 18, 2019 |
Deposit Date | Jan 7, 2020 |
Publicly Available Date | Jan 7, 2020 |
Journal | Scientific Reports |
Print ISSN | 2045-2322 |
Electronic ISSN | 2045-2322 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 9 |
Article Number | 16987 |
Pages | 1-11 |
DOI | https://doi.org/10.1038/s41598-019-53529-z |
Keywords | Multidisciplinary |
Public URL | https://nottingham-repository.worktribe.com/output/3081458 |
Publisher URL | https://www.nature.com/articles/s41598-019-53529-z |
Additional Information | Received: 25 March 2019; Accepted: 21 October 2019; First Online: 18 November 2019; : The authors declare no competing interests. |
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