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

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.

• Authors: 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
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 172 Issue 1 Pg. 61-68 (Nov 2018) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 30056565 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Cadherins
• Carrier Proteins
• Membrane Proteins
• RAPH1 protein, human
• Trastuzumab

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cadherins (genetics)
• Carrier Proteins (genetics)
• DNA Copy Number Variations
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lymphatic Metastasis
• Membrane Proteins (genetics)
• Middle Aged
• Neoplasm Grading
• Neoplasm Invasiveness (genetics, pathology)
• Prognosis
• Trastuzumab (therapeutic use)