PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer

Alfarsi, Lutfi H.; El Ansari, Rokaya; Craze, Madeleine L.; Masisi, Brendah K.; Ellis, Ian O.; Rakha, Emad A.; Green, Andrew R.

Abstract

Background
PPFIA1 is an important regulator of cell migration and invasion, regulating focal adhesion signalling and disassembly. PPFIA1 is frequently amplified in breast cancer, and recent functional studies indicate that PPFIA1 is an important promoter of migration and invasion in breast cancer. This study aims to evaluate the utility of PPFIA1 expression in the luminal breast cancer as a prognostic marker to predict the response to endocrine therapy.

Methods
Large, well-characterised cohorts of primary luminal breast cancer patients with long-term follow-up was assessed for the clinical impact of PPFIA1 expression at the transcriptomic and proteomic levels. Prognostic significance of PPFIA1 and its relationship with clinical outcome and benefit of endocrine therapy were analysed. In addition, its association with other related-genes was analysed.

Results
There was significant association between PPFIA1 expression and a member of the liprin family that involves in cell invasion (PPFIBPI), and the cell cycle regulator (CCND1), whereas a negative association was observed with the tumour suppressor gene (CD82). Patients with high PPFIA1 expression were associated with high risk of recurrence, distant metastasis and death from breast cancer (P< 0.05). Importantly, high PPFIA1 expression predicted relapse in a subset of patients who were subject to endocrine treatment alone, and was an independent prognostic marker of unfavourable outcome in these patients (P< 0.05).

Conclusions
These findings support the proposed role for PPFIA1 as a regulator of cell migration in breast cancer and provides definitive evidence for the clinical utility of PPFIA1 expression in patients with luminal breast cancer. Most importantly, our data suggests that PPFIA1 might be a potential predictive marker for poor benefit from endocrine therapy.

Citation

Alfarsi, L. H., El Ansari, R., Craze, M. L., Masisi, B. K., Ellis, I. O., Rakha, E. A., & Green, A. R. (2020). PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer. BMC Cancer, 20(1), https://doi.org/10.1186/s12885-020-06939-6

• Journal Article Type: Article
• Acceptance Date: May 7, 2020
• Online Publication Date: May 14, 2020
• Publication Date: May 14, 2020
• Deposit Date: May 12, 2020
• Publicly Available Date: May 14, 2020
• Journal: BMC Cancer
• Electronic ISSN: 1471-2407
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 1
• Article Number: 425
• DOI: https://doi.org/10.1186/s12885-020-06939-6
• Keywords: Breast cancer, oestrogen receptor, Endocrine resistance, PPFIA1, Liprin, Predictive biomarker, Genetics, Cancer Research, Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/4424839
• Publisher URL: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-06939-6
• Additional Information: Received: 24 February 2020; Accepted: 7 May 2020; First Online: 14 May 2020; : This study was performed according to the REMARK guidelines for tumour prognostic studies [CitationRef removed], and approved by the Nottingham Research Ethics Committee 2 under the title “Development of a molecular genetic classification of breast cancer”. All samples from Nottingham used in this study were pseudo-anonymised and collected prior to 2006 and therefore under the Human Tissue Act informed patient consent was not needed. Release of data was also pseudo-anonymised as per Human Tissue Act regulations.; : Not applicable.; : The authors declare that they have no competing interests.