Muslim L Alabdullah1,2*, Islam Miligy3,4, Adel Alblihy1, Reem Ali1, Michael Toss3, Stephen Chan1, Srinivasan Madhusudan1,5 and Emad A Rakha6
1Department of Translational Oncology, University of Nottingham Biodiscovery Institute, UK
2Department of Pediatric Surgery, Leicester University Teaching Hospitals NHS Trust, UK
3Nottingham Breast Cancer Research Centre, University of Nottingham, UK
4Department of Pathology, Menoufia University, Egypt
5Department of Oncology, Nottingham University Hospitals, UK
6Department of Academic Pathology, University of Nottingham Biodiscovery Institute, UK
Background: Cell signaling proteins play a crucial role in tumor behavior. ATM, PTEN, XIAP and p85α are key cell signaling biomarkers. This study evaluates the prognostic significance of those biomarkers in primary Ovarian Cancer (OC).
Methods: ATM, PTEN, XIAP and p85α expression was assessed immunohistochemically in a large primary OC cohort (n=525). Outcome analysis was evaluated using progression free and overall survival.
Results: High XIAP and p85α expression was associated with features of high-risk OC, including serous histology and higher residual tumor following surgery. P85α negative/low expression improved patients’ platinum sensitivity. Although overexpression of XIAP and p85α was associated with recurrence and poor outcome, upregulated PTEN expression improved outcome. ATM and
XIAP were independent prognostic factors in predicting shorter recurrence outcome. In patients with high ATM and XIAP expression, PTEN and p85α lost their significance on patients’ outcome.
Conclusion: ATM, PTEN, XIAP and p85α have crucial and different roles in OC progression and can potentially predict patients’ outcome. The data presented here reveal a novel network between the investigated proteins with vital clinical applications in OC. PTEN and p85α are more likely to behave in cell-specific contexts concerning ATM and XIAP expression status.
DNA Repair; PTEN; p85α; ATM; XIAP; Ovarian cancer; Prognosis
Alabdullah ML, Miligy I, Alblihy A, Ali R, Toss M, Chan S, et al. The Prognostic Significance of the Signaling Proteins: PTEN, P85α, ATM and XIAP in Primary Ovarian Cancer. Clin Oncol. 2021;6:1814..