Skip to main content

Research Repository

Advanced Search

Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer

Kurozumi, Sasagu; Joseph, Chitra; Sonbul, Sultan; Aleskandarany, Mohammed A.; Pigera, Marian; Alsaleem, Mansour; Alsaeed, Sami; Kariri, Yousif; Nolan, Christopher C.; Diez-Rodriguez, Maria; Johnston, Simon; Mongan, Nigel P.; Fujii, Takaaki; Shirabe, Ken; Martin, Stewart G.; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad A.


Sasagu Kurozumi

Sultan Sonbul

Mohammed A. Aleskandarany

Marian Pigera

Mansour Alsaleem

Sami Alsaeed

Yousif Kariri

Christopher C. Nolan

Maria Diez-Rodriguez

Simon Johnston

Takaaki Fujii

Ken Shirabe

Professor of Cancer and Radiation Biology

Professor of Breast Cancer Pathology


BACKGROUND: Ras association and pleckstrin homology domains 1 (RAPH1) is involved in cytoskeleton regulation and re-epithelialisation in invasive carcinoma and therefore may play a key role in carcinogenesis and metastasis. We herein investigated the biological and clinical significance of RAPH1 in breast cancer using large annotated cohorts.
METHODS: The clinicopathological and prognostic significance of RAPH1 was assessed at the genomic and transcriptomic levels using The Cancer Genome Atlas (TCGA) dataset (n=1039) and the results were validated using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n=1980). RAPH1 protein expression was evaluated by immunohistochemistry in a large, well-characterised cohort of early-stage breast cancer (n=1040).
RESULTS: In both the TCGA-BRCA and METABRIC cohorts, RAPH1 mRNA expression and RAPH1 copy number alteration were strongly correlated. RAPH1 mRNA overexpression was significantly correlated with high expression of adhesion and EMT markers including CDH1, TGFbeta1 and CD44. RAPH1 mRNA overexpression was a significant predictor of a poor prognosis (Hazard ratio: 3.88; p = 0.049). High RAPH1 protein expression was associated with higher grade tumours with high proliferation index, triple negative phenotype and high E-cadherin expression. High RAPH1 protein expression was an independent predictor of shorter survival (Hazard ratio: 4.37; p = 0.037).
CONCLUSIONS: High RAPH1 expression is correlated with aggressive breast cancer phenotypes and provides independent prognostic value in invasive breast cancer.


Kurozumi, S., Joseph, C., Sonbul, S., Aleskandarany, M. A., Pigera, M., Alsaleem, M., …Rakha, E. A. (2018). Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer. Breast Cancer Research and Treatment, 172(1), 61–68. doi:10.1007/s10549-018-4891-y

Journal Article Type Article
Acceptance Date Jun 6, 2018
Online Publication Date Jul 28, 2018
Publication Date 2018-11
Deposit Date Jul 17, 2018
Publicly Available Date Jul 29, 2019
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 1573-7217
Publisher Humana Press
Peer Reviewed Peer Reviewed
Volume 172
Issue 1
Pages 61–68
Keywords invasive breast cancer; lymphovascular invasion; ras association and pleckstrin homology domains 1; re-epithelialisation; E-cadherin
Public URL
Publisher URL
Copyright Statement Copyright information regarding this work can be found at the following address:
Additional Information This is a pre-print of an article published in Breast Cancer Research and Treatment. The final authenticated version is available online at:


You might also like

Downloadable Citations