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28.07.2018 | Preclinical study

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

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

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2018

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Abstract

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 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, TGFβ1 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.

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Titel: Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer
verfasst von: Sasagu Kurozumi
Chitra Joseph
Sultan Sonbul
Mohammed A. Aleskandarany
Marian Pigera
Mansour Alsaleem
Sami Alsaeed
Yousif Kariri
Christopher C. Nolan
Maria Diez-Rodriguez
Simon Johnston
Nigel P. Mongan
Takaaki Fujii
Ken Shirabe
Stewart G. Martin
Ian O. Ellis
Andrew R. Green
Emad A. Rakha
Publikationsdatum: 28.07.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4891-y

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Springer Medizin

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

Abstract

Background

Methods

Results

Conclusions

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Springer Medizin

Abstract

Background

Methods

Results

Conclusions

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